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
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
Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
Small RNAs(sRNAs)are important non-coding RNAs that usually play crucial roles in gene expression at the post-transcriptional level.The sRNAs have mostly been investigated in model microorganisms such as Escherichia c...Small RNAs(sRNAs)are important non-coding RNAs that usually play crucial roles in gene expression at the post-transcriptional level.The sRNAs have mostly been investigated in model microorganisms such as Escherichia coli and some pathogens.Nevertheless,microbial sRNAs from extreme environments such as the polar regions and deep sea have recently been discovered and analyzed for their unique roles in stress response,metabolic regulation and adaptation to extreme environments.These sRNAs fine-tune gene expression during oxidative and radiation stress,and modulate temperature and osmotic pressure responses.Representative sRNAs and their functions in thermophilic,psychrophilic,halophilic and radiation-tolerant bacteria are summarized in this review.Despite challenges in sample collection,RNA isolation,and functional annotation,the study of sRNAs in extreme environments provides opportunities for discovering novel regulatory mechanisms,applying them to biotechnology,and advancing our understanding of evolutionary adaptations.Looking ahead,high-throughput sequencing,synthetic biology,and multi-omics integration will bring new breakthroughs in discovering novel sRNAs and their functions and regulatory mechanisms.Such advancements are poised to enable comprehensive characterization of sRNA-mediated regulatory networks in extremophiles and unlock their biotechnological potential through mechanism-driven applications.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
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
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
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
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
Objectives:Prostate cancer(PCa)is a highly prevalent male malignancy with limited efficacy in advanced stages.Dysregulated modulation of necroptosis was reported to be tightly correlated with PCa initiation and progre...Objectives:Prostate cancer(PCa)is a highly prevalent male malignancy with limited efficacy in advanced stages.Dysregulated modulation of necroptosis was reported to be tightly correlated with PCa initiation and progression.Herein,we aimed to identify necroptosis-associated long non-coding RNAs(lncRNAs)and delineate their functional roles in PCa through an integrated approach combining bioinformatic analyses and in vitro experimental validation.Methods:RNA sequencing data and corresponding clinical information of PCa were downloaded from The Cancer Genome Atlas(TCGA).Differentially expressed necroptosis-related genes(NRGs)and lncRNAs were screened,and necroptosis activity was assessed by single-sample gene set enrichment analysis(ssGSEA).Weighted Gene Co-expression Network Analysis(WGCNA)identified necroptosis-related lncRNA modules,with key lncRNAs prioritized via Cox regression.Clinical correlation analyses and in vitro experiments validated the function of the key lncRNA LINC00595.Results:A total of 50 differentially expressed NRGs were identified,among which pro-necroptotic genes exhibited pronounced downregulation,while anti-necroptotic genes were significantly upregulated.Consistently,ssGSEA confirmed reduced necroptosis activity in PCa.WGCNA further identified 13 core necroptosis-related lncRNAs(NRlncRNAs),with Cox regression analysis pinpointing LINC00595 and LINC00908 as the top prognostic candidates.Both lncRNAs were downregulated in PCa,with low expression correlating with advanced T stage,lymph node metastasis,and poor prognosis.Functional experiments demonstrated that LINC00595 overexpression inhibited PCa cell proliferation,migration,and invasion,and enhanced necroptosis.Conclusions:Collectively,our findings identified LINC00595 and LINC00908 as novel regulators of necroptosis in PCa.Specifically,LINC00595 exerted tumor-suppressive effects by enhancing necroptosis,holding potential as prognostic biomarkers and therapeutic targets.展开更多
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 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 Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
基金supported by the National Natural Science Foundation of China(Grant nos.42476264,41976224).
文摘Small RNAs(sRNAs)are important non-coding RNAs that usually play crucial roles in gene expression at the post-transcriptional level.The sRNAs have mostly been investigated in model microorganisms such as Escherichia coli and some pathogens.Nevertheless,microbial sRNAs from extreme environments such as the polar regions and deep sea have recently been discovered and analyzed for their unique roles in stress response,metabolic regulation and adaptation to extreme environments.These sRNAs fine-tune gene expression during oxidative and radiation stress,and modulate temperature and osmotic pressure responses.Representative sRNAs and their functions in thermophilic,psychrophilic,halophilic and radiation-tolerant bacteria are summarized in this review.Despite challenges in sample collection,RNA isolation,and functional annotation,the study of sRNAs in extreme environments provides opportunities for discovering novel regulatory mechanisms,applying them to biotechnology,and advancing our understanding of evolutionary adaptations.Looking ahead,high-throughput sequencing,synthetic biology,and multi-omics integration will bring new breakthroughs in discovering novel sRNAs and their functions and regulatory mechanisms.Such advancements are poised to enable comprehensive characterization of sRNA-mediated regulatory networks in extremophiles and unlock their biotechnological potential through mechanism-driven applications.
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 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.
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 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 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.
文摘目的筛选并构建宫颈癌中与泛凋亡(PANoptosis)相关的长链非编码RNA(long non-coding RNA,lncRNA)预后模型。方法使用生物学数据库筛选出与泛凋亡相关的基因,结合宫颈癌转录组测序数据,筛选与泛凋亡基因表达相关的lncRNA,采用最小绝对值收缩与选择算子(least absolute shrinkage and selection operator,LASSO)-Cox回归分析,构建预后模型。根据模型对宫颈癌样本按风险评分分为高、低风险组。使用Kaplan-Meier、基因集富集分析(gene set enrichment analysis,GSEA)、ESTIMATE、CIBERSORT、Oncopredict等分析方法对高、低风险组进行差异分析。使用实时荧光逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)验证相关lncRNAs在宫颈癌组织和癌旁组织中的表达差异。结果成功构建包含11个lncRNAs的预后模型,分别是ARHGEF7-AS2、ASH1L-AS1、BASP1-AS1、C7orf66、CATIP-AS1、CYP4A22-AS1、DBH-AS1、DCST1-AS1、DGUOK-AS1、DPH6-DT、FLJ31104。高风险组患者总生存期较低风险组显著缩短(P<0.001)。模型在宫颈癌患者1、2、3年生存率预测中表现出良好效能,曲线下面积(area under the curve,AUC)分别为0.765(95%CI:0.705~0.825)、0.808(95%CI:0.728~0.868)和0.802(95%CI:0.732~0.852),且风险评分为独立预后因素。列线图预测宫颈癌患者1年期生存率为95%,2年期生存率为91%,而3年期生存率则下降至82%。低风险组患者免疫评分和ESTIMATE评分均高于高风险组(P<0.05)。低风险组CD+8T细胞、激活记忆CD+4 T细胞、调节性T细胞水平明显低于高风险组(P<0.05),休眠记忆CD+4 T细胞、激活肥大细胞、中性粒细胞水平明显高于高风险组(P<0.05)。Afuresertib、奥沙利铂、伏立诺他在高风险组中的药物耐药性较低风险组更强(P<0.05)。ARHGEF7-AS2和DBH-AS1在癌组织中的表达下调(P均<0.001),BASP1-AS1和CYP4A22-AS1在癌组织中的表达上调(P均<0.001)。结论构建的泛凋亡相关lncRNA预后模型能有效预测宫颈癌患者预后,并为个体化治疗提供潜在参考。
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Objectives:Prostate cancer(PCa)is a highly prevalent male malignancy with limited efficacy in advanced stages.Dysregulated modulation of necroptosis was reported to be tightly correlated with PCa initiation and progression.Herein,we aimed to identify necroptosis-associated long non-coding RNAs(lncRNAs)and delineate their functional roles in PCa through an integrated approach combining bioinformatic analyses and in vitro experimental validation.Methods:RNA sequencing data and corresponding clinical information of PCa were downloaded from The Cancer Genome Atlas(TCGA).Differentially expressed necroptosis-related genes(NRGs)and lncRNAs were screened,and necroptosis activity was assessed by single-sample gene set enrichment analysis(ssGSEA).Weighted Gene Co-expression Network Analysis(WGCNA)identified necroptosis-related lncRNA modules,with key lncRNAs prioritized via Cox regression.Clinical correlation analyses and in vitro experiments validated the function of the key lncRNA LINC00595.Results:A total of 50 differentially expressed NRGs were identified,among which pro-necroptotic genes exhibited pronounced downregulation,while anti-necroptotic genes were significantly upregulated.Consistently,ssGSEA confirmed reduced necroptosis activity in PCa.WGCNA further identified 13 core necroptosis-related lncRNAs(NRlncRNAs),with Cox regression analysis pinpointing LINC00595 and LINC00908 as the top prognostic candidates.Both lncRNAs were downregulated in PCa,with low expression correlating with advanced T stage,lymph node metastasis,and poor prognosis.Functional experiments demonstrated that LINC00595 overexpression inhibited PCa cell proliferation,migration,and invasion,and enhanced necroptosis.Conclusions:Collectively,our findings identified LINC00595 and LINC00908 as novel regulators of necroptosis in PCa.Specifically,LINC00595 exerted tumor-suppressive effects by enhancing necroptosis,holding potential as prognostic biomarkers and therapeutic targets.
