Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathologica...Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.展开更多
Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effec...Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.展开更多
A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiolog...A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.展开更多
Two non-coding transcripts of toxins were iso-lated from the venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch, named BmαTX15-SP and BmTXKβ-SP, respectively. Analysis of nucleotide sequences s...Two non-coding transcripts of toxins were iso-lated from the venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch, named BmαTX15-SP and BmTXKβ-SP, respectively. Analysis of nucleotide sequences shows that their 5’ sequences are identical to the 5 ’UTR and upstream open reading frame (ORF) sequences of the cDNAs encoding BmαTX15 and BmTXKb, two toxins from Buthus martensii Karsch. But no detectable homology exists in other regions. Two polyadenylated non-coding transcripts encode multiple short ORFs with no more than 34 amino acid resi-dues. The tailing signal (AATAAA) is situated at 14 or 18 bp downstream from the poly(A). The data of genomic se-quences provides support for Bmα TX15-SP and BmTXK β-SP not deriving from splicing errors of pre- mRNAs. Our finding provides evidence for the existence of non-sense-mediated mRNA decay (NMD) pathway in scorpion venom gland cells.展开更多
Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic ...Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.展开更多
Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-...Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.展开更多
Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular m...Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.展开更多
Long non-coding RNAs(lncRNAs)play a significant role in maintaining tissue morphology and functions,and their precise regulatory effectiveness is closely related to expression patterns.However,the spatial expression p...Long non-coding RNAs(lncRNAs)play a significant role in maintaining tissue morphology and functions,and their precise regulatory effectiveness is closely related to expression patterns.However,the spatial expression patterns of lncRNAs in humans are poorly characterized.Here,we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states.The lncRNA transcriptomes exhibited high consistency within the same tissues across resources,and even higher complexity in specialized tissues.Tissue-elevated(TE)lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis.We detected 1 to 4684 robust TE lncRNAs across tissues;the highest number was in testis tissue,followed by brain tissue.Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways.Moreover,we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues;TE lncRNAs also tended to be associated with cancer,and exhibited differential expression or were correlated with patient survival.In summary,spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.展开更多
BACKGROUND Spinal cord injury(SCI)is a severe and permanent trauma that often leads to significant motor,sensory,and autonomic dysfunction.Neuronal apoptosis is a major pathomechanism underlying secondary injury in SC...BACKGROUND Spinal cord injury(SCI)is a severe and permanent trauma that often leads to significant motor,sensory,and autonomic dysfunction.Neuronal apoptosis is a major pathomechanism underlying secondary injury in SCI.Long non-coding RNAs(lncRNAs)have emerged as key regulators of gene expression and cellular processes,including apoptosis.However,the role of lncRNA growth arrest-specific transcript 5(GAS5)in SCI-induced neuronal apoptosis remains unclear.AIM To investigate the role of lncRNA GAS5 in SCI-induced neuronal apoptosis via its interaction with microRNA(miR)-21 and the phosphatase and tensin homolog(PTEN)/AKT pathway.METHODS SCI rat models and hypoxic neuronal cell models were established.Motor function was assessed using the Basso-Beattie-Bresnahan score.Expression levels of GAS5,miR-21,PTEN,caspase 3,B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and AKT were measured using quantitative PCR or Western blot analysis.Neuronal apoptosis was determined by TUNEL staining.Dual-luciferase reporter assays validated GAS5-miR-21 binding.Knockdown and overexpression experiments explored the functional effects of the GAS5/miR-21 axis.RESULTS GAS5 was significantly upregulated in the spinal cord following SCI,coinciding with increased neuronal apoptosis and decreased AKT activation.In vitro experiments demonstrated that GAS5 acted as a molecular sponge for miR-21,leading to increased PTEN expression and inhibition of the AKT signaling pathway,thereby promoting apoptosis.In vivo,GAS5 knockdown attenuated neuronal apoptosis,enhanced AKT activation,and improved motor function recovery in SCI rats.CONCLUSION GAS5 promotes neuronal apoptosis in SCI by binding to miR-21 and upregulating PTEN expression,inhibiting the AKT pathway.Targeting GAS5 may represent a novel therapeutic strategy for SCI.展开更多
BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatoria...BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.展开更多
Non-coding RNAs(ncRNAs)play important roles in the regulation of many biological processes,such as transcription initiation and epigenetic modifications that occur after transcription and development.Several novel tra...Non-coding RNAs(ncRNAs)play important roles in the regulation of many biological processes,such as transcription initiation and epigenetic modifications that occur after transcription and development.Several novel transcripts have been identified via high-throughput sequencing.However,identifying ncRNAs among the transcripts of novel species using alignment-based features is difficult.Thus,developing a fast and accurate method based on alignment-free features to identify ncRNAs among novel transcripts is necessary.In this study,we proposed a new approach,namely,coding potential prediction based on alignment-free features(CPAF),to identify ncRNAs among a large number of candidates.CPAF used four types of features:Fickett score;Hexamer score;composition,transition,and distribution features;and modified k-mer.From the results,CPAF performed better than previous state-of-the-art methods in predicting ncRNA transcripts,with particular reference to small ncRNAs.Finally,we applied CPAF to identify ncRNAs in Pacific oyster transcripts.Our approach identified more ncRNAs than other previously used methods.展开更多
The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of inte...The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of intercellular communication,with their cargo of non-coding RNAs(ncRNAs)serving as key regulatory elements.This review examines the multifaceted roles of immune cell-derived exosomal ncRNAs in tumor biology.The involvement of various immune cells,including T cells,B cells,natural killer cells,macrophages,neutrophils,and myeloid-derived suppressor cells,in utilizing exosomal ncRNAs to regulate tumor initiation and progression is explored.Additionally,the biogenesis and delivery mechanisms of these immune cell-derived exosomal ncRNAs are discussed,alongside their potential clinical applications in cancer.展开更多
Matrix metalloproteinases(MMPs)are essential enzymes involved in extracellular matrix degradation and remodeling.Such processes are integral to normal tissue homeostasis and several pathological conditions such as can...Matrix metalloproteinases(MMPs)are essential enzymes involved in extracellular matrix degradation and remodeling.Such processes are integral to normal tissue homeostasis and several pathological conditions such as cancer.Among these MMPs,MMP-13 plays a key role in cancer progression,driving tumor invasion,metastasis,and angiogenesis.Despite significant advancements in understanding its biology,therapeutic targeting of MMP-13 remains challenging owing to its complex and multifaceted regulatory mechanisms.Recent studies have underscored the pivotal role of non-coding RNAs(ncRNAs),including long ncRNAs,microRNAs,and circular RNAs,in modulating MMP-13 expression.This review provides a comprehensive analysis of MMP-13 regulation by several signaling pathways,the influence of ncRNAs on these signaling pathways,and MMP-13 expression during cancer progression and metastasis.Furthermore,we explored the clinical relevance of ncRNA-mediated regulatory networks,highlighting their potential as diagnostic biomarkers and therapeutic targets in various cancers.By unraveling these regulatory mechanisms,this review offers valuable insights into innovative strategies for cancer diagnosis and treatment and emphasizes the translational significance of ncRNA-mediated MMP-13 regulation in oncology.展开更多
Background:Long non-coding RNAs are implicated in metabolic diseases and malignancies,but their role in multiple myeloma(MM)with type 2 diabetes mellitus(T2DM)remains unclear.This study evaluated Long non-coding RNA M...Background:Long non-coding RNAs are implicated in metabolic diseases and malignancies,but their role in multiple myeloma(MM)with type 2 diabetes mellitus(T2DM)remains unclear.This study evaluated Long non-coding RNA Morrbid expression in MM patients with/without T2DM.Methods:The study enrolled 107 MM patients(48 with T2DM,59 without)and 72 non-MM controls(23 with T2DM,49 without).Peripheral blood mononuclear cells(PBMCs)were isolated from whole blood samples using red blood cell lysis.Total RNA was extracted from PBMCs,followed by reverse transcription,and the expression levels of Morrbid were detected by Reverse transcription-quantitative PCR.Results:We found that the expression of Morrbid was upregulated in the MM group compared to the non-MM patients.Within the MM group,the expression of Morrbid was significantly higher in patients with T2DM than in those without T2DM.In contrast,no significant difference in Morrbid expression was observed between T2DM and non-T2DM patients in the non-MM patients.Furthermore,we discovered a positive correlation between Morrbid expression and fasting blood sugar levels in MM patients.Operating characteristic curve analysis revealed an area under the curve of 0.822(sensitivity 77.1%,specificity 79.7%)for diagnosing T2DM in MM,suggesting that Morrbid may serve as a novel diagnostic biomarker for T2DM in MM patients.Conclusions:The high expression of Morrbid in MM patients with T2DM may indicate its critical role in tumor-related glucose metabolism.Additionally,Morrbid may potentially serve as a diagnostic biomarker for T2DM in MM patients.展开更多
Mesenchymal stem cells(MSCs)are known for their ability to differentiate into various cell lineages,including osteoblasts(bone-forming cells),and for their significant paracrine effects.Among their secreted products,e...Mesenchymal stem cells(MSCs)are known for their ability to differentiate into various cell lineages,including osteoblasts(bone-forming cells),and for their significant paracrine effects.Among their secreted products,exosomes have gained considerable attention as nanoscale carriers of bioactive molecules such as non-coding RNAs(ncRNAs).These ncRNAs,including microRNAs,long ncRNAs,and circular ncRNAs,are critical regulators of gene expression and cellular functions.Moreover,MSC-derived exosomes not only offer advantages such as targeted delivery,reduced immunogenicity,and protection of cargo material,but also carry ncRNAs that have therapeutic and diagnostic potential in bone-related disorders.Emerging evidence has highlighted the role of MSC-derived exosomal ncRNAs in osteogenesis,bone remodeling,and intercellular signaling in the bone microenvironment.This review consolidates recent research on the role of MSC-derived exosomal ncRNAs in maintaining bone homeostasis and bone-related disorders via various signaling pathways and epigenetic modifications.Furthermore,we explore the therapeutic potential of MSC-derived exosomal ncRNAs as biomarkers and therapeutic targets.This comprehensive review offers key insights into the regulatory roles of MSC-derived exosomal ncRNAs in bone biology and their clinical significance in bone-related diseases.展开更多
Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolv...Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolves,the emergence of acquired resistance leads to treatment failure.Many researches have shown that non-coding RNAs(ncRNAs)not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer,mediating drug resistance by regulating multiple targets and pathways.In addition,the regulation of immune response by ncRNAs is dualistic,forming a microenvironment for inhibits/promotes immune escape through changes in the expression of immune checkpoints.The aim of this review is to understand the effects of ncRNAs on the occurrence and development of lung cancer,focusing on the role of ncRNAs in regulating drug resistance of lung cancer.展开更多
Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet c...Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet complex roles in GC,functioning as both tumor suppressors and promoters depending on the disease stage and context.Autophagy influences cellular homeostasis and metabolism,whereas lncRNAs regulate gene expression through epigenetic modifications,RNA sponging,and protein interactions.Notably,the interplay between lncRNAs and autophagy modulates tumor progression,metastasis,chemoresistance,and the tumor microenvironment.This study explored the intricate relationship between lncRNAs and autophagy in GC,highlighting their roles in pathogenesis and treatment resistance.By addressing current knowledge gaps and proposing innovative therapeutic strategies,we have emphasized the potential of targeting this dynamic interplay for improved diagnostic and therapeutic outcomes.展开更多
Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and c...Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and computed tomography scanning;however,their specificity and sensitivity are suboptimal.Despite significant advancements in HCC biomarker detection,the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis.Therefore,it is crucial to explore more sensitive HCC biomarkers for improved diagnosis,monitoring,and management of the disease.Long non-coding RNA(lncRNA)serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity.Moreover,investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC.We searched the PubMed database for literature,comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells.Furthermore,we prospectively summarize its potential implications in diagnosing and treating HCC.展开更多
Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutat...Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutations(ncDNMs)remains less understood.Here,we integrate cortex cell-specific cis-regulatory element annotations,a deep learning-based variant prediction model,and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection(SSC)and Autism Speaks MSSNG resource(MSSNG)cohorts.Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects,including 137 down-regulated regulatory mutations(DrMuts)and 101 up-regulated regulatory mutations(UrMuts).Subsequent association analyses reveal that only DrMuts regulating loss-of-function(LoF)intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD(Odds ratio=4.34;P=0.001).A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified,including 12 recognized and 29 unreported genes.Interestingly,these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations.Our study introduces an optimized approach for elucidating the functional roles of ncDNMs,thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.展开更多
Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant chall...Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant challenges due to the development of drug resistance.Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture,transfection,RNA immunoprecipitation,co-immunoprecipitation,and xenograft tumor models.They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC.This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1,which play critical roles in regulating KIF9-AS1.Furthermore,KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1,thereby enhancing stemness and contributing to sorafenib resistance in HCC cells.These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC,highlighting the need for further investigation into its clinical application potential.展开更多
文摘Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.
基金Supported by The Joint Fund of Zhejiang Provincial Natural Science Foundation of China,No.LKLY25H160002.
文摘Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.
基金supported by the National Natural Science Foundation of China,Nos.82171347,82371362the Natural Science Foundation of Hunan Province,No.2022JJ30971the Scientific Research Project of Hunan Provincial Health Commission of China,No.202204040024(all to GX).
文摘A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39970897).
文摘Two non-coding transcripts of toxins were iso-lated from the venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch, named BmαTX15-SP and BmTXKβ-SP, respectively. Analysis of nucleotide sequences shows that their 5’ sequences are identical to the 5 ’UTR and upstream open reading frame (ORF) sequences of the cDNAs encoding BmαTX15 and BmTXKb, two toxins from Buthus martensii Karsch. But no detectable homology exists in other regions. Two polyadenylated non-coding transcripts encode multiple short ORFs with no more than 34 amino acid resi-dues. The tailing signal (AATAAA) is situated at 14 or 18 bp downstream from the poly(A). The data of genomic se-quences provides support for Bmα TX15-SP and BmTXK β-SP not deriving from splicing errors of pre- mRNAs. Our finding provides evidence for the existence of non-sense-mediated mRNA decay (NMD) pathway in scorpion venom gland cells.
基金supported by the National Natural Science Foundation of China,Nos.82301486(to SL)and 82071325(to FY)Medjaden Academy&Research Foundation for Young Scientists,No.MJR202310040(to SL)+2 种基金Nanjing Medical University Science and Technique Development,No.NMUB20220060(to SL)Medical Scientific Research Project of Jiangsu Commission of Health,No.ZDA2020019(to JZ)Health China Buchang Zhiyuan Public Welfare Project for Heart and Brain Health,No.HIGHER202102(to QD).
文摘Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.
基金supported by the National Natural Science Foundation of China,No.81600747(to YD)the Start-Up Foundation for Doctors of Liaoning Province,China,No.201501020(to YD)。
文摘Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.
基金financially supported by the National Natural Science Foundation of China,No.81371366(to HFW)Characteristic Innovation Project of Colleges and Universities in Guangdong Province of China,No.2018KTSCX075(to HFW)+3 种基金the Key Project of Social Development of Dongguan of China,No.20185071521640(to HFW)College Students’ Science and Technology Innovation Training Project,China,Nos.201810571058,GDMU2018024,GDMU2018056,GDMU2018061(to HFW)College Students’ Innovative Experimental Project in Guangdong Medical University,China,No.ZZDS001(to HFW)College Students’ Science and Technology Innovation Cultivation Project in Guangdong of China,No.pdjh2019b0217(to HFW)
文摘Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.
基金This work was supported by the National Natural Science Foundation of China(Nos.31970646,32060152,32070673,and 32170676)the Hainan Province Science and Technology Special Fund(No.ZDYF2021SHFZ051)+2 种基金the Harbin Medical University Marshal Initiative Funding(No.HMUMIF-21024)the Marshal Initiative Funding of Hainan Medical University(No.JBGS202103)the Heilongjiang Touyan Innovation Team Program.
文摘Long non-coding RNAs(lncRNAs)play a significant role in maintaining tissue morphology and functions,and their precise regulatory effectiveness is closely related to expression patterns.However,the spatial expression patterns of lncRNAs in humans are poorly characterized.Here,we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states.The lncRNA transcriptomes exhibited high consistency within the same tissues across resources,and even higher complexity in specialized tissues.Tissue-elevated(TE)lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis.We detected 1 to 4684 robust TE lncRNAs across tissues;the highest number was in testis tissue,followed by brain tissue.Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways.Moreover,we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues;TE lncRNAs also tended to be associated with cancer,and exhibited differential expression or were correlated with patient survival.In summary,spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.
基金Supported by the Major Research Plan from the Health Commission of Hongkou District,No.2001-03Academic Subject Boosting Plan in the Shanghai Fourth People’s Hospital affiliated to Tongji University School of Medicine Shanghai,No.SY-XKZT-2020-1003.
文摘BACKGROUND Spinal cord injury(SCI)is a severe and permanent trauma that often leads to significant motor,sensory,and autonomic dysfunction.Neuronal apoptosis is a major pathomechanism underlying secondary injury in SCI.Long non-coding RNAs(lncRNAs)have emerged as key regulators of gene expression and cellular processes,including apoptosis.However,the role of lncRNA growth arrest-specific transcript 5(GAS5)in SCI-induced neuronal apoptosis remains unclear.AIM To investigate the role of lncRNA GAS5 in SCI-induced neuronal apoptosis via its interaction with microRNA(miR)-21 and the phosphatase and tensin homolog(PTEN)/AKT pathway.METHODS SCI rat models and hypoxic neuronal cell models were established.Motor function was assessed using the Basso-Beattie-Bresnahan score.Expression levels of GAS5,miR-21,PTEN,caspase 3,B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and AKT were measured using quantitative PCR or Western blot analysis.Neuronal apoptosis was determined by TUNEL staining.Dual-luciferase reporter assays validated GAS5-miR-21 binding.Knockdown and overexpression experiments explored the functional effects of the GAS5/miR-21 axis.RESULTS GAS5 was significantly upregulated in the spinal cord following SCI,coinciding with increased neuronal apoptosis and decreased AKT activation.In vitro experiments demonstrated that GAS5 acted as a molecular sponge for miR-21,leading to increased PTEN expression and inhibition of the AKT signaling pathway,thereby promoting apoptosis.In vivo,GAS5 knockdown attenuated neuronal apoptosis,enhanced AKT activation,and improved motor function recovery in SCI rats.CONCLUSION GAS5 promotes neuronal apoptosis in SCI by binding to miR-21 and upregulating PTEN expression,inhibiting the AKT pathway.Targeting GAS5 may represent a novel therapeutic strategy for SCI.
文摘BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.
基金supported by the National Natural Science Foundation of China(No.11701546).
文摘Non-coding RNAs(ncRNAs)play important roles in the regulation of many biological processes,such as transcription initiation and epigenetic modifications that occur after transcription and development.Several novel transcripts have been identified via high-throughput sequencing.However,identifying ncRNAs among the transcripts of novel species using alignment-based features is difficult.Thus,developing a fast and accurate method based on alignment-free features to identify ncRNAs among novel transcripts is necessary.In this study,we proposed a new approach,namely,coding potential prediction based on alignment-free features(CPAF),to identify ncRNAs among a large number of candidates.CPAF used four types of features:Fickett score;Hexamer score;composition,transition,and distribution features;and modified k-mer.From the results,CPAF performed better than previous state-of-the-art methods in predicting ncRNA transcripts,with particular reference to small ncRNAs.Finally,we applied CPAF to identify ncRNAs in Pacific oyster transcripts.Our approach identified more ncRNAs than other previously used methods.
基金supported by the National Natural Science Foundation of China(No.82203056)the Natural Science Foundation of Liaoning Province(No.2023-BS-167)+1 种基金the Science and Technology Talent Innovation Support Plan of Dalian(NO.2022RQ091)the“1+X”program for Clinical Competency enhancement-Clinical Research Incubation Project of the Second Hospital of Dalian Medical University(No.2022LCYJYB01)。
文摘The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of intercellular communication,with their cargo of non-coding RNAs(ncRNAs)serving as key regulatory elements.This review examines the multifaceted roles of immune cell-derived exosomal ncRNAs in tumor biology.The involvement of various immune cells,including T cells,B cells,natural killer cells,macrophages,neutrophils,and myeloid-derived suppressor cells,in utilizing exosomal ncRNAs to regulate tumor initiation and progression is explored.Additionally,the biogenesis and delivery mechanisms of these immune cell-derived exosomal ncRNAs are discussed,alongside their potential clinical applications in cancer.
基金Supported by the Anusandhan National Research Foundation,No.CRG/2023/000212.
文摘Matrix metalloproteinases(MMPs)are essential enzymes involved in extracellular matrix degradation and remodeling.Such processes are integral to normal tissue homeostasis and several pathological conditions such as cancer.Among these MMPs,MMP-13 plays a key role in cancer progression,driving tumor invasion,metastasis,and angiogenesis.Despite significant advancements in understanding its biology,therapeutic targeting of MMP-13 remains challenging owing to its complex and multifaceted regulatory mechanisms.Recent studies have underscored the pivotal role of non-coding RNAs(ncRNAs),including long ncRNAs,microRNAs,and circular RNAs,in modulating MMP-13 expression.This review provides a comprehensive analysis of MMP-13 regulation by several signaling pathways,the influence of ncRNAs on these signaling pathways,and MMP-13 expression during cancer progression and metastasis.Furthermore,we explored the clinical relevance of ncRNA-mediated regulatory networks,highlighting their potential as diagnostic biomarkers and therapeutic targets in various cancers.By unraveling these regulatory mechanisms,this review offers valuable insights into innovative strategies for cancer diagnosis and treatment and emphasizes the translational significance of ncRNA-mediated MMP-13 regulation in oncology.
基金Luzhou Municipal Government-Southwest Medical University Cooperation Application Foundation(Project No.:2023LZXNYDJ045)Luzhou Science and Technology Bureau,China(Project No.:2024JYJ064)Academic Research Projects of Southwest Medical University(Project No.:2023QN042&2024ZKY040)。
文摘Background:Long non-coding RNAs are implicated in metabolic diseases and malignancies,but their role in multiple myeloma(MM)with type 2 diabetes mellitus(T2DM)remains unclear.This study evaluated Long non-coding RNA Morrbid expression in MM patients with/without T2DM.Methods:The study enrolled 107 MM patients(48 with T2DM,59 without)and 72 non-MM controls(23 with T2DM,49 without).Peripheral blood mononuclear cells(PBMCs)were isolated from whole blood samples using red blood cell lysis.Total RNA was extracted from PBMCs,followed by reverse transcription,and the expression levels of Morrbid were detected by Reverse transcription-quantitative PCR.Results:We found that the expression of Morrbid was upregulated in the MM group compared to the non-MM patients.Within the MM group,the expression of Morrbid was significantly higher in patients with T2DM than in those without T2DM.In contrast,no significant difference in Morrbid expression was observed between T2DM and non-T2DM patients in the non-MM patients.Furthermore,we discovered a positive correlation between Morrbid expression and fasting blood sugar levels in MM patients.Operating characteristic curve analysis revealed an area under the curve of 0.822(sensitivity 77.1%,specificity 79.7%)for diagnosing T2DM in MM,suggesting that Morrbid may serve as a novel diagnostic biomarker for T2DM in MM patients.Conclusions:The high expression of Morrbid in MM patients with T2DM may indicate its critical role in tumor-related glucose metabolism.Additionally,Morrbid may potentially serve as a diagnostic biomarker for T2DM in MM patients.
基金Supported by Anusandhan National Research Foundation,No.CRG/2023/000212.
文摘Mesenchymal stem cells(MSCs)are known for their ability to differentiate into various cell lineages,including osteoblasts(bone-forming cells),and for their significant paracrine effects.Among their secreted products,exosomes have gained considerable attention as nanoscale carriers of bioactive molecules such as non-coding RNAs(ncRNAs).These ncRNAs,including microRNAs,long ncRNAs,and circular ncRNAs,are critical regulators of gene expression and cellular functions.Moreover,MSC-derived exosomes not only offer advantages such as targeted delivery,reduced immunogenicity,and protection of cargo material,but also carry ncRNAs that have therapeutic and diagnostic potential in bone-related disorders.Emerging evidence has highlighted the role of MSC-derived exosomal ncRNAs in osteogenesis,bone remodeling,and intercellular signaling in the bone microenvironment.This review consolidates recent research on the role of MSC-derived exosomal ncRNAs in maintaining bone homeostasis and bone-related disorders via various signaling pathways and epigenetic modifications.Furthermore,we explore the therapeutic potential of MSC-derived exosomal ncRNAs as biomarkers and therapeutic targets.This comprehensive review offers key insights into the regulatory roles of MSC-derived exosomal ncRNAs in bone biology and their clinical significance in bone-related diseases.
文摘Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolves,the emergence of acquired resistance leads to treatment failure.Many researches have shown that non-coding RNAs(ncRNAs)not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer,mediating drug resistance by regulating multiple targets and pathways.In addition,the regulation of immune response by ncRNAs is dualistic,forming a microenvironment for inhibits/promotes immune escape through changes in the expression of immune checkpoints.The aim of this review is to understand the effects of ncRNAs on the occurrence and development of lung cancer,focusing on the role of ncRNAs in regulating drug resistance of lung cancer.
文摘Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet complex roles in GC,functioning as both tumor suppressors and promoters depending on the disease stage and context.Autophagy influences cellular homeostasis and metabolism,whereas lncRNAs regulate gene expression through epigenetic modifications,RNA sponging,and protein interactions.Notably,the interplay between lncRNAs and autophagy modulates tumor progression,metastasis,chemoresistance,and the tumor microenvironment.This study explored the intricate relationship between lncRNAs and autophagy in GC,highlighting their roles in pathogenesis and treatment resistance.By addressing current knowledge gaps and proposing innovative therapeutic strategies,we have emphasized the potential of targeting this dynamic interplay for improved diagnostic and therapeutic outcomes.
基金Supported by Science Project of Hunan Provincial Healthy Commission,No.20230844.
文摘Hepatocellular carcinoma(HCC)is the predominant form of primary liver cancer,accounting for 90%of all cases.Currently,early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection,B-ultrasound,and computed tomography scanning;however,their specificity and sensitivity are suboptimal.Despite significant advancements in HCC biomarker detection,the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis.Therefore,it is crucial to explore more sensitive HCC biomarkers for improved diagnosis,monitoring,and management of the disease.Long non-coding RNA(lncRNA)serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity.Moreover,investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC.We searched the PubMed database for literature,comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells.Furthermore,we prospectively summarize its potential implications in diagnosing and treating HCC.
基金supported by the National Natural Science of China(82322032 and 82221005)the Outstanding Youth Foundation of Jiangsu Province(BK20220050)+4 种基金the National Key Research&Development(R&D)Program of China(2024YFC2706800 and 2021YFC2700600)the Major Project of Changzhou Medical Center(CZKY1040101)the Major Project of Taizhou Clinical Medical College(TZKY20240003)the Major Program of Gusu School(GSKY20210102)the China Postdoctoral Science Foundation(2024M760296).
文摘Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutations(ncDNMs)remains less understood.Here,we integrate cortex cell-specific cis-regulatory element annotations,a deep learning-based variant prediction model,and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection(SSC)and Autism Speaks MSSNG resource(MSSNG)cohorts.Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects,including 137 down-regulated regulatory mutations(DrMuts)and 101 up-regulated regulatory mutations(UrMuts).Subsequent association analyses reveal that only DrMuts regulating loss-of-function(LoF)intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD(Odds ratio=4.34;P=0.001).A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified,including 12 recognized and 29 unreported genes.Interestingly,these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations.Our study introduces an optimized approach for elucidating the functional roles of ncDNMs,thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.
基金Supported by National Natural Science Foundation of China,No.82405223Yunling Scholars Program,No.XDYC-YLXZ-2022-0027.
文摘Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant challenges due to the development of drug resistance.Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture,transfection,RNA immunoprecipitation,co-immunoprecipitation,and xenograft tumor models.They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC.This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1,which play critical roles in regulating KIF9-AS1.Furthermore,KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1,thereby enhancing stemness and contributing to sorafenib resistance in HCC cells.These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC,highlighting the need for further investigation into its clinical application potential.
