Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the reg...Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the regulatory mechanisms governing flavonoid biosynthesis in fruits.Phytohormones are involved in the regulation of flavonoid biosynthesis.The abscisic acid,ethylene,jasmonic acid,cytokinins,and brassinosteroids promote flavonoid biosynthesis,while auxin negatively regulates flavonoid biosynthesis.Subsequently,transcription factors from the MYB,bHLH,WRKY,NAC,and bZIP families are pivotal in regulating flavonoid biosynthesis.In addition,non-coding RNAs(microRNA and lncRNA)also participate in the regulation of flavonoids biosynthesis.MicroRNAs are generally believed to negatively regulate flavonoid metabolism in fruits,while lncRNAs have the opposite effect.Furthermore,the interactions between plant hormones,transcription factors,and non-coding RNAs in fruit flavonoid biosynthesis were analyzed.Ultimately,a foundational regulatory network for fruit flavonoid biosynthesis was hereby established.展开更多
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
Genomic destabilization and defective DNA repair are the most prominent features of tumour cells and are exploited by various chemotherapy drugs for cancer therapy.Long non-coding RNA(lncR-NAs)have emerged as powerful...Genomic destabilization and defective DNA repair are the most prominent features of tumour cells and are exploited by various chemotherapy drugs for cancer therapy.Long non-coding RNA(lncR-NAs)have emerged as powerful regulators of gene expression and are thus involved in diverse biological processes.Recent studies have demonstrated that several lncRNAs play critical roles in DNA repair.Nonetheless,the relationship between DNA damage-responsive lncRNAs and chemoresistance remains poorly defined.In this study,we established four different DNA damage models triggered by cisplatin(DDP),H2O2,neocarzinostatin(NCS)or ultraviolet(UV)irradiation and identified a specific upregu-lated lncRNA(lnc-DUSP6)involved in the cisplatin-induced DNA damage response.Furthermore,loss-or gain-of-function experiments confirmed that lnc-DUSP6 enhanced DNA repair and cell survival under cisplatin treatment,thus promoting cisplatin resistance.Mechanistically,an RNA immunoprecipitation(RIP)assay revealed that lnc-DUSP6 directly interacts with DUSP6(Dual Specificity Phosphatase 6),which is closely associated with cisplatin sensitivity.Additionally,overexpression of DUSP6 significantly rescued the effects of lnc-DUSP6 silencing on DNA repair and cell survival under cisplatin treatment.O-verall,our results show the effect and underlying mechanism of lnc-DUSP6 in cisplatin resistance:lnc-DUSP6 promotes cisplatin-induced DNA damage repair and cisplatin resistance by stabilizing DUSP6,which is highly clinically important for enhancing the efficacy of cisplatin for cancers.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
Anther is a key male reproductive organ that is essential for the plant life cycle,from the sporophyte to the gametophyte generation.To explore the isoform-level transcriptional landscape of developing anthers in maiz...Anther is a key male reproductive organ that is essential for the plant life cycle,from the sporophyte to the gametophyte generation.To explore the isoform-level transcriptional landscape of developing anthers in maize(Zea mays L.),we analyzed Iso-Seq data from anthers collected at 10 developmental stages,together with strand-specific RNA-seq,CAGE-seq,and PAS-seq data.Of the 152,026 high-confidence full-length isoforms identified,68.8%have not been described;these include 22,365 isoforms that originate from previously unannotated loci and 82,167 novel isoforms that originate from annotated protein-coding genes.Using our newly developed strategy to detect dynamic expression patterns of isoforms,we identify 13,899 differentially variable regions(DVRs);surprisingly,1275 genes contain more than two DVRs,revealing highly efficient utilization of limited genic regions.We identify 7876 long non-coding RNAs(lncRNAs)from 4098 loci,most of which were preferentially expressed during cell differentiation and meiosis.We also detected 371 long-range interactions involving intergenic lncRNAs(lincRNAs);interestingly,243 were lincRNA-gene ones,and the interacting genes were highly expressed in anthers,suggesting that many potential lncRNA regulators of key genes are required for anther development.This study provides valuable resources and fundamental information for studying the essential transcripts of key genes during anther development.展开更多
Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functi...Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functional diversity of RP11-derived lncRNAs—originally mapped to bacterial artificial chromosome(BAC)clones from the Roswell Park Cancer Institute—has only recently begun to be appreciated.This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC,outlining their genomic origins,molecular mechanisms,and biological significance.We highlight their roles in metabolic reprogramming,microRNA network modulation,and tumor progression,as well as their diagnostic and prognostic value in tissue and serum-based analyses.Finally,we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.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
Background:Tibetan chickens,a unique native breed in the Qinghai-Tibet Plateau of China,possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment.Increasing evidence sugge...Background:Tibetan chickens,a unique native breed in the Qinghai-Tibet Plateau of China,possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment.Increasing evidence suggests that long non-coding RNAs(lncRNAs)and microRNAs(miRNAs)play roles in the hypoxic adaptation of high-altitude animals,although their exact involvement remains unclear.Results:This study aimed to elucidate the global landscape of mRNAs,lncRNAs,and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs(ceRNAs)and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos.In total,354 differentially expressed genes(DE genes),389 differentially expressed lncRNAs(DE lncRNAs),and 73 differentially expressed miRNAs(DE miRNAs)were identified between Tibetan chickens(TC)and control Chahua chickens(CH).GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis(including blood vessel development and blood circulation)and energy metabolism(including glucose,carbohydrate,and lipid metabolism).The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions,which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens.Conclusions:Analysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism.These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.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
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
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
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
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
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
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
基金supported by the China Agricultural Research System(Grant No.CARS-09)the Central Government Guiding Local Science and Technology Development Project(Grant No.YDZX2023029)the Gansu Planning Projects on Science and Technology(Grant No.23CXNJ0013).
文摘Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the regulatory mechanisms governing flavonoid biosynthesis in fruits.Phytohormones are involved in the regulation of flavonoid biosynthesis.The abscisic acid,ethylene,jasmonic acid,cytokinins,and brassinosteroids promote flavonoid biosynthesis,while auxin negatively regulates flavonoid biosynthesis.Subsequently,transcription factors from the MYB,bHLH,WRKY,NAC,and bZIP families are pivotal in regulating flavonoid biosynthesis.In addition,non-coding RNAs(microRNA and lncRNA)also participate in the regulation of flavonoids biosynthesis.MicroRNAs are generally believed to negatively regulate flavonoid metabolism in fruits,while lncRNAs have the opposite effect.Furthermore,the interactions between plant hormones,transcription factors,and non-coding RNAs in fruit flavonoid biosynthesis were analyzed.Ultimately,a foundational regulatory network for fruit flavonoid biosynthesis was hereby established.
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 National Natural Science Foundation of China(No.82071571)the Natural Science Foundation of Guangdong Province(No.2021A1515010601)+3 种基金Guangdong Provincial Basic and Applied Basic Research Foundation-Dongguan Joint Fund(No.2024A1515140121)the“Climbing”Program of Guangdong Province(No.pdjh2021b0226)the Innovation and Entrepreneurship Program for College Students(No.GDMU2022038,202310571038,ZZDC002,S202510571041)Guangdong Medical University Undergraduate Innovation and Entrepreneurship Education Base Project(No.JDXM2024039,JDXM2025046)。
文摘Genomic destabilization and defective DNA repair are the most prominent features of tumour cells and are exploited by various chemotherapy drugs for cancer therapy.Long non-coding RNA(lncR-NAs)have emerged as powerful regulators of gene expression and are thus involved in diverse biological processes.Recent studies have demonstrated that several lncRNAs play critical roles in DNA repair.Nonetheless,the relationship between DNA damage-responsive lncRNAs and chemoresistance remains poorly defined.In this study,we established four different DNA damage models triggered by cisplatin(DDP),H2O2,neocarzinostatin(NCS)or ultraviolet(UV)irradiation and identified a specific upregu-lated lncRNA(lnc-DUSP6)involved in the cisplatin-induced DNA damage response.Furthermore,loss-or gain-of-function experiments confirmed that lnc-DUSP6 enhanced DNA repair and cell survival under cisplatin treatment,thus promoting cisplatin resistance.Mechanistically,an RNA immunoprecipitation(RIP)assay revealed that lnc-DUSP6 directly interacts with DUSP6(Dual Specificity Phosphatase 6),which is closely associated with cisplatin sensitivity.Additionally,overexpression of DUSP6 significantly rescued the effects of lnc-DUSP6 silencing on DNA repair and cell survival under cisplatin treatment.O-verall,our results show the effect and underlying mechanism of lnc-DUSP6 in cisplatin resistance:lnc-DUSP6 promotes cisplatin-induced DNA damage repair and cisplatin resistance by stabilizing DUSP6,which is highly clinically important for enhancing the efficacy of cisplatin for cancers.
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supported by the Excellent Young Scientists Fund(Category B)(32422063)the National Key Research and Development Program of China(2022YFF1003500)the Zhengzhou University Qiushi Postdoctoral Research Funding Program.For open access,the authors have applied for a Creative Commons Attribution(CC BY)license for any Author Accepted Manuscript version arising from this submission.
文摘Anther is a key male reproductive organ that is essential for the plant life cycle,from the sporophyte to the gametophyte generation.To explore the isoform-level transcriptional landscape of developing anthers in maize(Zea mays L.),we analyzed Iso-Seq data from anthers collected at 10 developmental stages,together with strand-specific RNA-seq,CAGE-seq,and PAS-seq data.Of the 152,026 high-confidence full-length isoforms identified,68.8%have not been described;these include 22,365 isoforms that originate from previously unannotated loci and 82,167 novel isoforms that originate from annotated protein-coding genes.Using our newly developed strategy to detect dynamic expression patterns of isoforms,we identify 13,899 differentially variable regions(DVRs);surprisingly,1275 genes contain more than two DVRs,revealing highly efficient utilization of limited genic regions.We identify 7876 long non-coding RNAs(lncRNAs)from 4098 loci,most of which were preferentially expressed during cell differentiation and meiosis.We also detected 371 long-range interactions involving intergenic lncRNAs(lincRNAs);interestingly,243 were lincRNA-gene ones,and the interacting genes were highly expressed in anthers,suggesting that many potential lncRNA regulators of key genes are required for anther development.This study provides valuable resources and fundamental information for studying the essential transcripts of key genes during anther development.
基金supported by the National Research Foundation of Korea(NRF),funded by the Ministry of Science and ICT(MSIT),Republic of Korea(grant numbers:RS-2022-NR070489 and RS-2023-00210847)the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health and Welfare,Republic of Korea(grant number HR21C1003).
文摘Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functional diversity of RP11-derived lncRNAs—originally mapped to bacterial artificial chromosome(BAC)clones from the Roswell Park Cancer Institute—has only recently begun to be appreciated.This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC,outlining their genomic origins,molecular mechanisms,and biological significance.We highlight their roles in metabolic reprogramming,microRNA network modulation,and tumor progression,as well as their diagnostic and prognostic value in tissue and serum-based analyses.Finally,we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.
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supported by the National Natural Science Foundation of China(31972532)the China Agricultural Research System(CARS-40-K05)the Innovation Base Cu。
文摘Background:Tibetan chickens,a unique native breed in the Qinghai-Tibet Plateau of China,possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment.Increasing evidence suggests that long non-coding RNAs(lncRNAs)and microRNAs(miRNAs)play roles in the hypoxic adaptation of high-altitude animals,although their exact involvement remains unclear.Results:This study aimed to elucidate the global landscape of mRNAs,lncRNAs,and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs(ceRNAs)and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos.In total,354 differentially expressed genes(DE genes),389 differentially expressed lncRNAs(DE lncRNAs),and 73 differentially expressed miRNAs(DE miRNAs)were identified between Tibetan chickens(TC)and control Chahua chickens(CH).GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis(including blood vessel development and blood circulation)and energy metabolism(including glucose,carbohydrate,and lipid metabolism).The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions,which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens.Conclusions:Analysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism.These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.
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.
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.
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.
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.
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.
