Colorectal cancer(CRC)remains a formidable global health challenge and is associated with dismal survival outcomes and high mortality among patients diagnosed at advanced stages.Despite advancements in early screening...Colorectal cancer(CRC)remains a formidable global health challenge and is associated with dismal survival outcomes and high mortality among patients diagnosed at advanced stages.Despite advancements in early screening and therapeutic interventions,the outcomes of patients with advanced-stage CRC remain suboptimal,as these patients continue to exhibit a persistently low 5-year survival rate.Palliative radiotherapy(RT)is crucial for advanced CRC patients,but radioresistance remains a significant clinical challenge.This resistance is attributed to multiple mechanisms,such as genetic heterogeneity,dysregulated DNA damage repair and tumor microenvironment metabolic disorders.Recent studies have shown that noncoding RNAs(ncRNAs),mainly microRNAs,long ncRNAs(lncRNAs)and circular RNAs,play pivotal roles in regulating CRC radiosensitivity through diverse mechanisms,such as epithelial-mesenchymal transition,epigenetic reprogramming,posttranscriptional regulation and oncogenic signaling pathway activation.For example,microRNAs such as miR-141-3p and miR-630 enhance CRC radiosensitivity by targeting oncogenic pathways.In addition,lncRNAs,including the lncRNAs HOTAIR and LINC00630,influence the radiosensitivity of CRC through interactions with the DNA damage repair machinery and epigenetic modulators,respectively.In addition,circ_0124554 acts as a competitive endogenous RNA to regulate oncogenic signaling.ncRNAs also serve as potential biomarkers for predicting radiosensitivity and prognosis.This review synthesizes the current evidence on the ncRNA-mediated regulatory networks that influence CRC radiosensitivity,emphasizing their potential as therapeutic targets to overcome RT resistance and improve outcomes in advanced CRC.By bridging mechanistic insights with clinical applications,this work aims to guide future research and the implementation of precision RT strategies.展开更多
Background:Transmural heterogeneity of the transient outward potassium current(I_(to))is a major contributor to J-wave syndrome(JWS).However,the underlying molecular mechanisms remain elusive.The present study aimed t...Background:Transmural heterogeneity of the transient outward potassium current(I_(to))is a major contributor to J-wave syndrome(JWS).However,the underlying molecular mechanisms remain elusive.The present study aimed to investigate the role of cardiac injury-related bclaf1-interacting lncRNA(lncCIRBIL)in JWS and to delineate the molecular mechanisms.Methods:Whole-cell patch-clamp techniques were used to record ionic currents and action potentials(APs).Protein and mRNA expression related to I_(to)current were assessed.RNA immunoprecipitation,RNA Pulldown,mRNA stability,and decapping assays were performed to dissect the underlying mechanisms.Results:Plasma lncCIRBIL levels were significantly reduced in JWS patients and cold-induced JWS mice.Knockout of lncCIRBIL increased the incidence of J-wave and the susceptibility to ventricular arrhythmia in mice.In lncCIRBIL-deficient mice,the transmural gradient of Kv4.2 expression and I_(to)current density was markedly enhanced in the right ventricle,but not the left ventricle.In contrast,cardiomyocyte-specific transgenic overexpression of lncCIRBIL produced the opposite effects.In human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the conserved human homologous fragment of lncCIRBIL(hcf-CIRBIL)suppressed I_(to),attenuated the AP notch,and prolonged APD20.Mechanistically,lncCIRBIL directly binds to up-frameshift protein1(UPF1),promoting KCND2 mRNA decay by enhancing its decapping.Conclusions:LncCIRBIL modulates the transmural heterogeneity of KCND2 expression by regulating UPF1-mediated mRNA decay.Inhibition of lncCIRBIL exacerbates JWS by enhancing right ventricular I_(to)heterogeneity,whereas its overexpression exerts protective effects.These findings identify lncCIRBIL as a potential therapeutic target for J-wave syndrome.展开更多
The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research...The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.展开更多
Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not ...Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not all aspects due to the heterogeneity of the disorder have been determined yet.In this review,we focus on the recent findings and summarize the current data on epigenetic mechanisms such as DNA methylation and different metabolites produced during methylation and demethylation and various types of small noncoding RNAs involved in the pathogenesis of different groups of NOA.展开更多
Liver diseases are progressive conditions driven by multiple factors,including molecular regulators such as nonprotein-coding RNAs,which orchestrate genetic and epigenetic processes across various biological levels.Lo...Liver diseases are progressive conditions driven by multiple factors,including molecular regulators such as nonprotein-coding RNAs,which orchestrate genetic and epigenetic processes across various biological levels.Long noncoding RNAs(lncRNAs),RNA molecules longer than 200 nucleotides,have been identified as key modulators in both cancerous and noncancerous liver diseases.Among them,taurine-upregulated gene 1(TUG1),one of the earliest discovered lncRNAs,has emerged as a tumor promoter in hepatocellular carcinoma.Functionally,TUG1 exerts its regulatory effects primarily through microRNA sponging as a competing endogenous RNA while also exhibiting protein-binding capabilities that suggest additional roles in both transcriptional and posttranscriptional regulation.Furthermore,evidence suggests that dysregulation of TUG1 is closely linked to the development and progression of liver diseases.This review explores the key characteristics,mechanisms,and signaling pathways through which TUG1 affects liver disease,offering fresh insights into potential therapeutic directions and new avenues for future TUG1-related research.展开更多
The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,N...The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,No.6,2018,pp.869–878.展开更多
Malignant tumors are heterogeneous diseases characterized by uncontrolled cell proliferation,invasion,metastasis,and/or recurrence of their malignancies.In particular,cancer stem cells(CSCs)within these tumors might b...Malignant tumors are heterogeneous diseases characterized by uncontrolled cell proliferation,invasion,metastasis,and/or recurrence of their malignancies.In particular,cancer stem cells(CSCs)within these tumors might be responsible for the property of invasiveness and/or therapies-resistance.CSCs are a self-renewing,awfully tumorigenic subpopulation of cancer cells,which are notorious for strong chemoresistance and are frequently responsible the aggravated invasion,metastasis,and/or recurrence.Developing targeting therapies against CSCs,therefore,may be deliberated a more encouraging mission for the greater cancer therapy.Innovation for a more potent anti-CSC treatment has been required as soon as possible.Interestingly,vitamin D could modulate the inflammatory condition of the tumor microenvironment(TME)by successfully affecting CSCs,which has an imperative role in determining the malignant phenotype of CSCs.In addition,vitamin D may also contribute to the regulation of the malignant behaviors of CSCs.Consistently,vitamin D could have potential applications for the significant inhibition of several tumor growths within various cancer therapies.The biological significance of vitamin D for CSCs regulation may be involved in the function of APRO family proteins.Therefore,vitamin D could be one of the innovative therapeutic modalities for the development of novel CSCs related tumor therapies.展开更多
BACKGROUND Acute lung injury(ALI)is a fatal and heterogeneous disease.While bone marrow mesenchymal stem cells(BMSCs)have shown promise in ALI repair,their efficacy is compromised by a high apoptotic percentage.Prelim...BACKGROUND Acute lung injury(ALI)is a fatal and heterogeneous disease.While bone marrow mesenchymal stem cells(BMSCs)have shown promise in ALI repair,their efficacy is compromised by a high apoptotic percentage.Preliminary findings have indicated that long noncoding RNA(lncRNA)-ENST expression is markedly downregulated in MSCs under ischemic and hypoxic conditions,establishing a rationale for in vitro exploration.AIM To elucidate the role of lncRNA-ENST00000517482(lncRNA-ENST)in modulating MSC apoptosis.METHODS Founded on ALI in BEAS-2B cells with lipopolysaccharide,this study employed a transwell co-culture system to study BMSC tropism.BMSCs were genetically modified to overexpress or knockdown lncRNA-ENST.After analyzing the effects on autophagy,apoptosis and cell viability,the lncRNA-ENST/miR-539/c-MYC interaction was confirmed by dual-luciferase assays.RESULTS These findings have revealed a strong correlation between lncRNA-ENST levels and the apoptotic and autophagic status of BMSCs.On the one hand,the overexpression of lncRNA-ENST,as determined by Cell Counting Kit-8 assays,increased the expression of autophagy markers LC3B,ATG7,and ATG5.On the other hand,it reduced apoptosis and boosted BMSC viability.In co-cultures with BEAS-2B cells,lncRNA-ENST overexpression also improved cell vitality.Additionally,by downregulating miR-539 and upregulating c-MYC,lncRNA-ENST was found to influence mitochondrial membrane potential,enhance BMSC autophagy,mitigate apoptosis and lower the secretion of proinflammatory cytokines interleukin-6 and interleukin-1β.Collectively,within the in vitro framework,these results have highlighted the therapeutic potential of BMSCs in ALI and the pivotal regulatory role of lncRNA-ENST in miR-539 and apoptosis in lipopolysaccharide-stimulated BEAS-2B cells.CONCLUSION Our in vitro results show that enhanced lncRNA ENST expression can promote BMSC proliferation and viability by modulating the miR-539/c-MYC axis,reduce apoptosis and induce autophagy,which has suggested its therapeutic potential in the treatment of ALI.展开更多
Ferroptosis,an iron-dependent form of programmed cell death,has garnered significant attention in tumor research in recent years.Its core characteristics include aberrant accumulation of lipid peroxides and impairment...Ferroptosis,an iron-dependent form of programmed cell death,has garnered significant attention in tumor research in recent years.Its core characteristics include aberrant accumulation of lipid peroxides and impairment of antioxidant defense mechanisms,such as dysfunction of glutathione peroxidase 4.These fea-tures are closely intertwined with the initiation,progression,and therapeutic resistance of hepatocellular carcinoma(HCC).This review presents a systematic overview of the fundamental molecular mechanisms underlying ferroptosis,en-compassing iron metabolism,lipid metabolism,and the antioxidant system.Fur-thermore,it summarizes the potential applications of targeting ferroptosis in liver cancer treatment,including the mechanisms of action of anticancer agents(e.g.,sorafenib)and relevant ferroptosis-related enzymes.Against the backdrop of the growing potential of artificial intelligence(AI)in liver cancer research,various AI-based predictive models for liver cancer are being increasingly developed.On the one hand,this review examines the mechanisms of ferroptosis in HCC to explore novel early detection markers for liver cancer,to provide new insights for the development of AI-based early diagnostic models.On the other hand,it syn-thesizes the current research progress of existing liver cancer predictive models while summarizing key challenges that AI predictive models may encounter in the diagnosis and treatment of HCC.展开更多
Bone is a highly calcified and vascularized tissue.The vascular system plays a vital role in supporting bone growth and repair,such as the provision of nutrients,growth factors,and metabolic waste transfer.Moreover,th...Bone is a highly calcified and vascularized tissue.The vascular system plays a vital role in supporting bone growth and repair,such as the provision of nutrients,growth factors,and metabolic waste transfer.Moreover,the additional functions of the bone vasculature,such as the secretion of various factors and the regulation of bone-related signaling pathways,are essential for maintaining bone health.In the bone microenvironment,bone tissue cells play a critical role in regulating angiogenesis,including osteoblasts,bone marrow mesenchymal stem cells(BMSCs),and osteoclasts.Osteogenesis and bone angiogenesis are closely linked.The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis.Long noncoding RNAs(lncRNAs)are involved in various physiological processes,including osteogenesis and angiogenesis.Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis.However,the mechanism by which lncRNAs regulate angiogenesis-osteogenesis crosstalk remains unclear.In this review,we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health,aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.展开更多
The treatment of complex wounds presents a significant clinical challenge due to the limited availability of standardized therapeutic options.Adipose-derived stem cell exosomes(ADSC-Exos)are promising for their capabi...The treatment of complex wounds presents a significant clinical challenge due to the limited availability of standardized therapeutic options.Adipose-derived stem cell exosomes(ADSC-Exos)are promising for their capabilities to enhance angiogenesis,mitigate oxidative stress,modulate inflammatory pathways,support skin cell regeneration,and promote epithelialization.These exosomes deliver noncoding RNAs,including microRNAs,long non-coding RNAs,and circular RNAs,which facilitate collagen remodeling,reduce scar formation,and expedite wound healing.This study reviews the mechanisms,therapeutic roles,and challenges of non-coding RNA-loaded ADSC-Exos in wound healing and identifies critical directions for future research.It aims to provide insights for researchers into the potential mechanisms and clinical applications of ADSC-Exos non-coding RNAs in wound healing.展开更多
The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI...The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI:10.3727/096504016X14822800040451 URL:https://www.techscience.com/or/v25n6/56885 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.展开更多
BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads ...BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads to resistance through poorly characterized underlying molecular mechanisms.The long noncoding RNA SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion,prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil(5-Fu)resistance in CRC.AIM To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.METHODS Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 in CRC tissues from 225-Fu-sensitive patients and 145-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells.Cell viability and apoptosis were assessed in SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Furesistant CRC cells.SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model.SNHG5 interactions with microRNAs were predicted by bioinformatics analysis.Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b.Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein(Pgp)axis.RESULTS SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells.In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability,whereas SNHG5 knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment.In a xenograft mouse model,we confirmed that SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo.Mechanistically,SNHG5 acted as a molecular sponge for miR-26b.Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.CONCLUSION SNHG5/miR-26b/Pgp regulates CRC chemosensitivity,providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.展开更多
The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology ...The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology Research,Vol.28,No.1,2020,pp.65-73.展开更多
This editorial highlights the critical role of viral RNA signatures encapsulated within circulating exosomes as a potential missing link in the early diagnosis of gastrointestinal(GI)cancers.Current diagnostic methods...This editorial highlights the critical role of viral RNA signatures encapsulated within circulating exosomes as a potential missing link in the early diagnosis of gastrointestinal(GI)cancers.Current diagnostic methods for virus-associated GI malignancies often fall short in detecting infections at subclinical or pre-cancerous stages.We propose that viral RNA-loaded exosomes,by offering stable,specific,and non-invasive biomarkers,can bridge this gap and revolutionize early de-tection compared to conventional approaches.As highlighted by Zhang et al in their recent review,viral infections,such as hepatitis B and C viruses,Epstein-Barr virus,and human papillomavirus,are well-established contributors to the pathogenesis of various GI malignancies.However,current diagnostic methods often underperform in detecting these infections at subclinical or pre-cancerous stages.We highlight the shared points between virology,exosome biology,and oncology,reinforcing the importance of viral RNA-loaded exosomes as a“missing link”in the early detection of virus-associated GI cancers.We also discuss current challenges,translational opportunities,and the requirements for clinical vali-dation of these promising biomarkers.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-codin...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-coding RNA semaphorin 6Aantisense RNA 1(SEMA6A-AS1)was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.AIM To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.METHODS The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction,immunohistochemistry and Western blot.A growth curve,colony formation,wound-healing and transwell(with or without Matrigel)assays were respectively performed to assess the proliferation,migration and invasion abilities of HCC cells.Cell cycle and apoptosis assays were performed by flow cytometry.To investigate the potential mechanism underpinning SEMA6A-AS1,we utilized tagged RNA affinity purification,dual luciferase reporter assay and immunofluorescence.RESULTS Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression.SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level,high Edmondson-Steiner grade and poor prognosis.SEMA6A-AS1 significantly inhibited the proliferation,migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation.SEMA6A protein promoted the proliferation,migration and invasion of HCC cells by regulating the actin cytoskeleton.CONCLUSION Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation.SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.展开更多
Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced ra...Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.展开更多
The phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway is one of the most frequently dysregulated signaling networks in oral squamous cell carcinoma(OSCC).Although the tumor microenvironment(TME)and epig...The phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway is one of the most frequently dysregulated signaling networks in oral squamous cell carcinoma(OSCC).Although the tumor microenvironment(TME)and epigenetic modifiers are recognized to play a pivotal role in aberrant activation of the PI3K/AKT pathway in OSCC,the available evidence is fragmentary and a comprehensive analysis is warranted.This review evaluates the intricate mechanisms by which various components of the TME facilitate proliferation,apoptosis evasion,invasion,migration,angiogenesis,metastasis,as well as therapy resistance in OSCC through activation of PI3K/AKT signalling.The review has also analysed how epigenetic modifiers such as DNA methylation,histone modifications,and noncoding RNAs that have emerged as key players in orchestrating OSCC development and progression influence the PI3K/AKT pathway.Preclinical studies and clinical trials on the efficacy of PI3K/AKT inhibitors as viable options for OSCC treatment are discussed.Overall,this review supports the tenet that the PI3K/AKT pathway,which functions as a central hub through crosstalk with several oncogenic signaling pathways and overarching impact on all the hallmark traits of cancer,offers immense potential as a biomarker and oncotherapeutic target for OSCC.展开更多
OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was establishe...OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.展开更多
The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understoo...The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.展开更多
文摘Colorectal cancer(CRC)remains a formidable global health challenge and is associated with dismal survival outcomes and high mortality among patients diagnosed at advanced stages.Despite advancements in early screening and therapeutic interventions,the outcomes of patients with advanced-stage CRC remain suboptimal,as these patients continue to exhibit a persistently low 5-year survival rate.Palliative radiotherapy(RT)is crucial for advanced CRC patients,but radioresistance remains a significant clinical challenge.This resistance is attributed to multiple mechanisms,such as genetic heterogeneity,dysregulated DNA damage repair and tumor microenvironment metabolic disorders.Recent studies have shown that noncoding RNAs(ncRNAs),mainly microRNAs,long ncRNAs(lncRNAs)and circular RNAs,play pivotal roles in regulating CRC radiosensitivity through diverse mechanisms,such as epithelial-mesenchymal transition,epigenetic reprogramming,posttranscriptional regulation and oncogenic signaling pathway activation.For example,microRNAs such as miR-141-3p and miR-630 enhance CRC radiosensitivity by targeting oncogenic pathways.In addition,lncRNAs,including the lncRNAs HOTAIR and LINC00630,influence the radiosensitivity of CRC through interactions with the DNA damage repair machinery and epigenetic modulators,respectively.In addition,circ_0124554 acts as a competitive endogenous RNA to regulate oncogenic signaling.ncRNAs also serve as potential biomarkers for predicting radiosensitivity and prognosis.This review synthesizes the current evidence on the ncRNA-mediated regulatory networks that influence CRC radiosensitivity,emphasizing their potential as therapeutic targets to overcome RT resistance and improve outcomes in advanced CRC.By bridging mechanistic insights with clinical applications,this work aims to guide future research and the implementation of precision RT strategies.
基金supported by National Natural Science Foundation of China(82270320 to Yin D C,82300280 to Jin X X,82070344,81870295 to Pan Z W)HMU Marshal Initiative Funding(HMUMIF-21017 to Pan Z W)Excellent Young Medical Talents Training Fund of the First Affiliated Hospital of Harbin Medical University(No.2024YQ03 to Jin X X).
文摘Background:Transmural heterogeneity of the transient outward potassium current(I_(to))is a major contributor to J-wave syndrome(JWS).However,the underlying molecular mechanisms remain elusive.The present study aimed to investigate the role of cardiac injury-related bclaf1-interacting lncRNA(lncCIRBIL)in JWS and to delineate the molecular mechanisms.Methods:Whole-cell patch-clamp techniques were used to record ionic currents and action potentials(APs).Protein and mRNA expression related to I_(to)current were assessed.RNA immunoprecipitation,RNA Pulldown,mRNA stability,and decapping assays were performed to dissect the underlying mechanisms.Results:Plasma lncCIRBIL levels were significantly reduced in JWS patients and cold-induced JWS mice.Knockout of lncCIRBIL increased the incidence of J-wave and the susceptibility to ventricular arrhythmia in mice.In lncCIRBIL-deficient mice,the transmural gradient of Kv4.2 expression and I_(to)current density was markedly enhanced in the right ventricle,but not the left ventricle.In contrast,cardiomyocyte-specific transgenic overexpression of lncCIRBIL produced the opposite effects.In human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the conserved human homologous fragment of lncCIRBIL(hcf-CIRBIL)suppressed I_(to),attenuated the AP notch,and prolonged APD20.Mechanistically,lncCIRBIL directly binds to up-frameshift protein1(UPF1),promoting KCND2 mRNA decay by enhancing its decapping.Conclusions:LncCIRBIL modulates the transmural heterogeneity of KCND2 expression by regulating UPF1-mediated mRNA decay.Inhibition of lncCIRBIL exacerbates JWS by enhancing right ventricular I_(to)heterogeneity,whereas its overexpression exerts protective effects.These findings identify lncCIRBIL as a potential therapeutic target for J-wave syndrome.
文摘The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.
文摘Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not all aspects due to the heterogeneity of the disorder have been determined yet.In this review,we focus on the recent findings and summarize the current data on epigenetic mechanisms such as DNA methylation and different metabolites produced during methylation and demethylation and various types of small noncoding RNAs involved in the pathogenesis of different groups of NOA.
文摘Liver diseases are progressive conditions driven by multiple factors,including molecular regulators such as nonprotein-coding RNAs,which orchestrate genetic and epigenetic processes across various biological levels.Long noncoding RNAs(lncRNAs),RNA molecules longer than 200 nucleotides,have been identified as key modulators in both cancerous and noncancerous liver diseases.Among them,taurine-upregulated gene 1(TUG1),one of the earliest discovered lncRNAs,has emerged as a tumor promoter in hepatocellular carcinoma.Functionally,TUG1 exerts its regulatory effects primarily through microRNA sponging as a competing endogenous RNA while also exhibiting protein-binding capabilities that suggest additional roles in both transcriptional and posttranscriptional regulation.Furthermore,evidence suggests that dysregulation of TUG1 is closely linked to the development and progression of liver diseases.This review explores the key characteristics,mechanisms,and signaling pathways through which TUG1 affects liver disease,offering fresh insights into potential therapeutic directions and new avenues for future TUG1-related research.
文摘The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,No.6,2018,pp.869–878.
文摘Malignant tumors are heterogeneous diseases characterized by uncontrolled cell proliferation,invasion,metastasis,and/or recurrence of their malignancies.In particular,cancer stem cells(CSCs)within these tumors might be responsible for the property of invasiveness and/or therapies-resistance.CSCs are a self-renewing,awfully tumorigenic subpopulation of cancer cells,which are notorious for strong chemoresistance and are frequently responsible the aggravated invasion,metastasis,and/or recurrence.Developing targeting therapies against CSCs,therefore,may be deliberated a more encouraging mission for the greater cancer therapy.Innovation for a more potent anti-CSC treatment has been required as soon as possible.Interestingly,vitamin D could modulate the inflammatory condition of the tumor microenvironment(TME)by successfully affecting CSCs,which has an imperative role in determining the malignant phenotype of CSCs.In addition,vitamin D may also contribute to the regulation of the malignant behaviors of CSCs.Consistently,vitamin D could have potential applications for the significant inhibition of several tumor growths within various cancer therapies.The biological significance of vitamin D for CSCs regulation may be involved in the function of APRO family proteins.Therefore,vitamin D could be one of the innovative therapeutic modalities for the development of novel CSCs related tumor therapies.
基金Supported by the Peak Supporting Clinical Discipline of Shanghai Health Bureau,No.2023ZDFC0104the National Key R&D Program of China,No.2019YFA0110601.
文摘BACKGROUND Acute lung injury(ALI)is a fatal and heterogeneous disease.While bone marrow mesenchymal stem cells(BMSCs)have shown promise in ALI repair,their efficacy is compromised by a high apoptotic percentage.Preliminary findings have indicated that long noncoding RNA(lncRNA)-ENST expression is markedly downregulated in MSCs under ischemic and hypoxic conditions,establishing a rationale for in vitro exploration.AIM To elucidate the role of lncRNA-ENST00000517482(lncRNA-ENST)in modulating MSC apoptosis.METHODS Founded on ALI in BEAS-2B cells with lipopolysaccharide,this study employed a transwell co-culture system to study BMSC tropism.BMSCs were genetically modified to overexpress or knockdown lncRNA-ENST.After analyzing the effects on autophagy,apoptosis and cell viability,the lncRNA-ENST/miR-539/c-MYC interaction was confirmed by dual-luciferase assays.RESULTS These findings have revealed a strong correlation between lncRNA-ENST levels and the apoptotic and autophagic status of BMSCs.On the one hand,the overexpression of lncRNA-ENST,as determined by Cell Counting Kit-8 assays,increased the expression of autophagy markers LC3B,ATG7,and ATG5.On the other hand,it reduced apoptosis and boosted BMSC viability.In co-cultures with BEAS-2B cells,lncRNA-ENST overexpression also improved cell vitality.Additionally,by downregulating miR-539 and upregulating c-MYC,lncRNA-ENST was found to influence mitochondrial membrane potential,enhance BMSC autophagy,mitigate apoptosis and lower the secretion of proinflammatory cytokines interleukin-6 and interleukin-1β.Collectively,within the in vitro framework,these results have highlighted the therapeutic potential of BMSCs in ALI and the pivotal regulatory role of lncRNA-ENST in miR-539 and apoptosis in lipopolysaccharide-stimulated BEAS-2B cells.CONCLUSION Our in vitro results show that enhanced lncRNA ENST expression can promote BMSC proliferation and viability by modulating the miR-539/c-MYC axis,reduce apoptosis and induce autophagy,which has suggested its therapeutic potential in the treatment of ALI.
基金Supported by Henan Provincial Science and Technology Research Project,No.252102311168 and No.242102310066the Medical Education Research Project in Henan Province,No.WJLX2024153.
文摘Ferroptosis,an iron-dependent form of programmed cell death,has garnered significant attention in tumor research in recent years.Its core characteristics include aberrant accumulation of lipid peroxides and impairment of antioxidant defense mechanisms,such as dysfunction of glutathione peroxidase 4.These fea-tures are closely intertwined with the initiation,progression,and therapeutic resistance of hepatocellular carcinoma(HCC).This review presents a systematic overview of the fundamental molecular mechanisms underlying ferroptosis,en-compassing iron metabolism,lipid metabolism,and the antioxidant system.Fur-thermore,it summarizes the potential applications of targeting ferroptosis in liver cancer treatment,including the mechanisms of action of anticancer agents(e.g.,sorafenib)and relevant ferroptosis-related enzymes.Against the backdrop of the growing potential of artificial intelligence(AI)in liver cancer research,various AI-based predictive models for liver cancer are being increasingly developed.On the one hand,this review examines the mechanisms of ferroptosis in HCC to explore novel early detection markers for liver cancer,to provide new insights for the development of AI-based early diagnostic models.On the other hand,it syn-thesizes the current research progress of existing liver cancer predictive models while summarizing key challenges that AI predictive models may encounter in the diagnosis and treatment of HCC.
基金supported by the National Natural Science Foundation of China(No.81901430)the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515010379)+1 种基金the Science and Technology Projects in Guangzhou(No.2023A04J0555)the Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion(No.2021B1212040014),China.
文摘Bone is a highly calcified and vascularized tissue.The vascular system plays a vital role in supporting bone growth and repair,such as the provision of nutrients,growth factors,and metabolic waste transfer.Moreover,the additional functions of the bone vasculature,such as the secretion of various factors and the regulation of bone-related signaling pathways,are essential for maintaining bone health.In the bone microenvironment,bone tissue cells play a critical role in regulating angiogenesis,including osteoblasts,bone marrow mesenchymal stem cells(BMSCs),and osteoclasts.Osteogenesis and bone angiogenesis are closely linked.The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis.Long noncoding RNAs(lncRNAs)are involved in various physiological processes,including osteogenesis and angiogenesis.Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis.However,the mechanism by which lncRNAs regulate angiogenesis-osteogenesis crosstalk remains unclear.In this review,we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health,aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.
基金Supported by the Intra-Hospital Project of No.940 Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army,No.2021yxky016.
文摘The treatment of complex wounds presents a significant clinical challenge due to the limited availability of standardized therapeutic options.Adipose-derived stem cell exosomes(ADSC-Exos)are promising for their capabilities to enhance angiogenesis,mitigate oxidative stress,modulate inflammatory pathways,support skin cell regeneration,and promote epithelialization.These exosomes deliver noncoding RNAs,including microRNAs,long non-coding RNAs,and circular RNAs,which facilitate collagen remodeling,reduce scar formation,and expedite wound healing.This study reviews the mechanisms,therapeutic roles,and challenges of non-coding RNA-loaded ADSC-Exos in wound healing and identifies critical directions for future research.It aims to provide insights for researchers into the potential mechanisms and clinical applications of ADSC-Exos non-coding RNAs in wound healing.
文摘The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI:10.3727/096504016X14822800040451 URL:https://www.techscience.com/or/v25n6/56885 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.
基金Supported by the National Natural Science Foundation of China,No.82404088China Postdoctoral Science Foundation,No.2023M730587Changshu Talent Scientific Project,No.KCH202304.
文摘BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads to resistance through poorly characterized underlying molecular mechanisms.The long noncoding RNA SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion,prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil(5-Fu)resistance in CRC.AIM To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.METHODS Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 in CRC tissues from 225-Fu-sensitive patients and 145-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells.Cell viability and apoptosis were assessed in SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Furesistant CRC cells.SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model.SNHG5 interactions with microRNAs were predicted by bioinformatics analysis.Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b.Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein(Pgp)axis.RESULTS SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells.In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability,whereas SNHG5 knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment.In a xenograft mouse model,we confirmed that SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo.Mechanistically,SNHG5 acted as a molecular sponge for miR-26b.Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.CONCLUSION SNHG5/miR-26b/Pgp regulates CRC chemosensitivity,providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.
文摘The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology Research,Vol.28,No.1,2020,pp.65-73.
基金Supported by the Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘This editorial highlights the critical role of viral RNA signatures encapsulated within circulating exosomes as a potential missing link in the early diagnosis of gastrointestinal(GI)cancers.Current diagnostic methods for virus-associated GI malignancies often fall short in detecting infections at subclinical or pre-cancerous stages.We propose that viral RNA-loaded exosomes,by offering stable,specific,and non-invasive biomarkers,can bridge this gap and revolutionize early de-tection compared to conventional approaches.As highlighted by Zhang et al in their recent review,viral infections,such as hepatitis B and C viruses,Epstein-Barr virus,and human papillomavirus,are well-established contributors to the pathogenesis of various GI malignancies.However,current diagnostic methods often underperform in detecting these infections at subclinical or pre-cancerous stages.We highlight the shared points between virology,exosome biology,and oncology,reinforcing the importance of viral RNA-loaded exosomes as a“missing link”in the early detection of virus-associated GI cancers.We also discuss current challenges,translational opportunities,and the requirements for clinical vali-dation of these promising biomarkers.
基金Supported by Natural Science Foundation of Hunan Province,No.2021JJ41048 and No.S2019JJQNJJ2012and Changsha Natural Science Foundation,No.kq2208400.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-coding RNA semaphorin 6Aantisense RNA 1(SEMA6A-AS1)was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.AIM To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.METHODS The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction,immunohistochemistry and Western blot.A growth curve,colony formation,wound-healing and transwell(with or without Matrigel)assays were respectively performed to assess the proliferation,migration and invasion abilities of HCC cells.Cell cycle and apoptosis assays were performed by flow cytometry.To investigate the potential mechanism underpinning SEMA6A-AS1,we utilized tagged RNA affinity purification,dual luciferase reporter assay and immunofluorescence.RESULTS Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression.SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level,high Edmondson-Steiner grade and poor prognosis.SEMA6A-AS1 significantly inhibited the proliferation,migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation.SEMA6A protein promoted the proliferation,migration and invasion of HCC cells by regulating the actin cytoskeleton.CONCLUSION Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation.SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.
基金Open access funding provided by The Science,Technology&Innovation Funding Authority(STDF)in coop eration with The Egyptian Knowledge Bank(EKB).
文摘Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.
文摘The phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway is one of the most frequently dysregulated signaling networks in oral squamous cell carcinoma(OSCC).Although the tumor microenvironment(TME)and epigenetic modifiers are recognized to play a pivotal role in aberrant activation of the PI3K/AKT pathway in OSCC,the available evidence is fragmentary and a comprehensive analysis is warranted.This review evaluates the intricate mechanisms by which various components of the TME facilitate proliferation,apoptosis evasion,invasion,migration,angiogenesis,metastasis,as well as therapy resistance in OSCC through activation of PI3K/AKT signalling.The review has also analysed how epigenetic modifiers such as DNA methylation,histone modifications,and noncoding RNAs that have emerged as key players in orchestrating OSCC development and progression influence the PI3K/AKT pathway.Preclinical studies and clinical trials on the efficacy of PI3K/AKT inhibitors as viable options for OSCC treatment are discussed.Overall,this review supports the tenet that the PI3K/AKT pathway,which functions as a central hub through crosstalk with several oncogenic signaling pathways and overarching impact on all the hallmark traits of cancer,offers immense potential as a biomarker and oncotherapeutic target for OSCC.
文摘OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.
基金supported by the National Key Research and Development Program(2022YFA1104401)Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226-000041)+3 种基金Beijing Municipal Govemment(Beijing Scholar Program,PXM2021-014226-000020)National Natural Science Foundation of China(82030031,92149301,81991504,L2224038,82270945)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Chinese Research Unit of Tooth Development and Regeneration,Academy of Medical Sciences(2019-12M-5-031).
文摘The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
