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
Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathologica...Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.展开更多
Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effec...Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.展开更多
A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiolog...A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.展开更多
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
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
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
目的运用meta分析方法系统评价补肾方剂治疗男性不育症患者精子DNA损伤(SDF)的有效性和安全性。方法从中国知网、维普、万方、PubMed、Cochrane Library、Embase、Web of Science数据库中检索补肾方剂改善SDF的随机对照试验(RCT)研究,...目的运用meta分析方法系统评价补肾方剂治疗男性不育症患者精子DNA损伤(SDF)的有效性和安全性。方法从中国知网、维普、万方、PubMed、Cochrane Library、Embase、Web of Science数据库中检索补肾方剂改善SDF的随机对照试验(RCT)研究,对文献进行方法学质量评价,运用RevMan5.3.5软件进行meta分析,并对结局指标进行GRADE质量分级。结果共纳入17项RCT研究,涉及2164例男性患者。与西医常规治疗相比,补肾方剂能够显著改善男性不育症患者DNA碎片指数(DFI)(MD=-6.50,95%CI:-7.88~-5.11,P<0.01),提高配偶妊娠率(RR=2.11,95%CI:1.12~4.00,P=0.87)、精子总活率(MD=5.56,95%CI:4.39~6.74,P<0.01)、前向运动精子百分率(MD=6.82,95%CI:5.62~8.03,P<0.01)、精子浓度(MD=6.51,95%CI:3.81~9.21,P<0.01)和正常形态精子百分率(MD=1.26,95%CI:0.45~2.06,P<0.01),且补肾方剂不会增加不良反应的发生。结论低到中等质量证据表明,与西医常规治疗相比,补肾方剂在改善男性不育症患者DFI、精液参数、配偶妊娠率等方面具有一定优势,且安全性较好。展开更多
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.
文摘Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.
基金Supported by The Joint Fund of Zhejiang Provincial Natural Science Foundation of China,No.LKLY25H160002.
文摘Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.
基金supported by the National Natural Science Foundation of China,Nos.82171347,82371362the Natural Science Foundation of Hunan Province,No.2022JJ30971the Scientific Research Project of Hunan Provincial Health Commission of China,No.202204040024(all to GX).
文摘A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.
基金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 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.
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.
文摘目的运用meta分析方法系统评价补肾方剂治疗男性不育症患者精子DNA损伤(SDF)的有效性和安全性。方法从中国知网、维普、万方、PubMed、Cochrane Library、Embase、Web of Science数据库中检索补肾方剂改善SDF的随机对照试验(RCT)研究,对文献进行方法学质量评价,运用RevMan5.3.5软件进行meta分析,并对结局指标进行GRADE质量分级。结果共纳入17项RCT研究,涉及2164例男性患者。与西医常规治疗相比,补肾方剂能够显著改善男性不育症患者DNA碎片指数(DFI)(MD=-6.50,95%CI:-7.88~-5.11,P<0.01),提高配偶妊娠率(RR=2.11,95%CI:1.12~4.00,P=0.87)、精子总活率(MD=5.56,95%CI:4.39~6.74,P<0.01)、前向运动精子百分率(MD=6.82,95%CI:5.62~8.03,P<0.01)、精子浓度(MD=6.51,95%CI:3.81~9.21,P<0.01)和正常形态精子百分率(MD=1.26,95%CI:0.45~2.06,P<0.01),且补肾方剂不会增加不良反应的发生。结论低到中等质量证据表明,与西医常规治疗相比,补肾方剂在改善男性不育症患者DFI、精液参数、配偶妊娠率等方面具有一定优势,且安全性较好。
