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
Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepa...Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix.Advanced fibrosis could lead to cirrhosis and even liver cancer,which has become a significant health burden worldwide.Many studies have revealed that noncoding RNAs(ncRNAs),including microRNAs,long noncoding RNAs and circular RNAs,are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-βpathway,phosphatidylinositol 3-kinase/protein kinase B pathway,and Wnt/β-catenin pathway.NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis.NcRNAs mimics,ncRNAs in mesenchymal stem cell-derived exosomes,and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis.In this review,we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis,and discuss the potentials and challenges to use these ncRNAs for diagnosis,staging and treatment of liver fibrosis.All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.展开更多
Embryonic stem cells （ESCs） hold great promises for treating and studying numerous devastating diseases. The molecular basis of their potential is not completely understood. Large noncoding RNAs （lncRNAs） are an i...Embryonic stem cells （ESCs） hold great promises for treating and studying numerous devastating diseases. The molecular basis of their potential is not completely understood. Large noncoding RNAs （lncRNAs） are an important class of gene regulators that play essential roles in a variety of physiologic and pathologic processes. Dozens of lncRNAs are now identified to control ESC self-renewal and differentiation. Research on lncRNAs may provide novel insights into manipulating the cell fate or reprogramming somatic cells into induced pluripotent stem cells （iPSCs）. In this review, we summarize the recent research efforts in identifying functional lncRNAs and understanding how they act in ESCs, and discuss various future directions of this field.展开更多
Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conven...Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer （CRPC）, which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs （IncRNAs） have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding （not translated into proteins）. They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of IncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of IncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets.展开更多
Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological pr...Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.展开更多
Long noncoding RNAs(lncRNAs)are important regulators of cell processes that are usually dysregulated in gastric cancer(GC).Based on their high specificity and ease of detection in tissues and body fluids,increasing at...Long noncoding RNAs(lncRNAs)are important regulators of cell processes that are usually dysregulated in gastric cancer(GC).Based on their high specificity and ease of detection in tissues and body fluids,increasing attention has spurred the study of the roles of lncRNAs in GC patients.Thus,it is necessary to elucidate the molecular mechanisms and further explore the clinical applications of lncRNAs in GC.In this review,we summarize current knowledge to examine dysregulated lncRNAs in GC and their underlying molecular mechanisms and activities in GC,which involve microRNA sponging,mRNA stability,genetic variants,alternative splicing,transcription factor binding,and epigenetic modification.More significantly,the potential of lncRNAs as prognostic,circulating,and drug-resistant biomarkers for GC is also described.This review highlights the method of dissecting molecular mechanisms to explore the clinical application of lncRNAs in GC.Overall,this review offers assistance in using lncRNAs as novel candidates for molecular mechanisms and for the identification of revolutionary biomarkers for GC.展开更多
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common causeof chronic liver disorder worldwide. It represents a spectrum that includes acontinuum of different clinical entities ranging from simple st...Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common causeof chronic liver disorder worldwide. It represents a spectrum that includes acontinuum of different clinical entities ranging from simple steatosis to nonalcoholicsteatohepatitis, which can evolve to cirrhosis and in some cases tohepatocellular carcinoma, ultimately leading to liver failure. The pathogenesis ofNAFLD and the mechanisms underlying its progression to more pathologicalstages are not completely understood. Besides genetic factors, evidence indicatesthat epigenetic mechanisms occurring in response to environmental stimuli alsocontribute to the disease risk. Noncoding RNAs (ncRNAs), including microRNAs,long noncoding RNAs, and circular RNAs, are one of the epigenetic factors thatplay key regulatory roles in the development of NAFLD. As the field of ncRNAsis rapidly evolving, the present review aims to explore the current state ofknowledge on the roles of these RNA species in the pathogenesis of NAFLD,highlight relevant mechanisms by which some ncRNAs can modulate regulatorynetworks implicated in NAFLD, and discuss key challenges and future directionsfacing current research in the hopes of developing ncRNAs as next-generationnon-invasive diagnostics and therapies in NAFLD and subsequent progression tohepatocellular carcinoma.展开更多
Long non-coding RNAs(lnc RNAs), a newly discovered class of nc RNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that ...Long non-coding RNAs(lnc RNAs), a newly discovered class of nc RNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lnc RNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lnc RNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lnc RNAs, and evaluate the p o t e n t i a l r o l e s o f l n c R N A s a s n o v e l d i a g n o s t i c biomarkers and therapeutic targets in gastrointestinal cancer.展开更多
Several diverse long noncoding RNAs(lncRNAs)have been identified to be involved in hepatitis B virus(HBV)replication and oncogenesis,especially those dysregulated in HBV-related hepatocellular carcinoma(HCC).Most of t...Several diverse long noncoding RNAs(lncRNAs)have been identified to be involved in hepatitis B virus(HBV)replication and oncogenesis,especially those dysregulated in HBV-related hepatocellular carcinoma(HCC).Most of these dysregulated lncRNAs are modulated by the HBV X protein.The regulatory mechanisms of some lncRNAs in HBV replication and oncogenesis have been characterized.Genetic polymorphisms of several lncRNAs affecting HBV replication or oncogenesis have also been studied.The prognosis of HCC remains poor.It is important to identify novel tumor markers for early diagnosis and find more therapeutic targets for effective treatments of HCC.Some dysregulated lncRNAs in HBV-related HCC may become biomarkers for early diagnosis and/or the therapeutic targets of HCC.This mini-review summarizes these findings briefly,focusing on recent developments.展开更多
The incidence rates of hepatocellular carcinoma(HCC)have increased in recent decades.Despite advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain poor.Long noncoding RNAs...The incidence rates of hepatocellular carcinoma(HCC)have increased in recent decades.Despite advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain poor.Long noncoding RNAs(lncRNAs)and lipid metabolism play crucial roles in the development and progression of HCC.Enhanced lipid synthesis promotes HCC progression,and lncRNAs can reprogram the expression of lipogenic enzymes.Consequently,lipid metabolism-related(LMR)-lncRNAs regulate lipid anabolism,accelerating the onset and progression of HCC.This suggests that LMR-lncRNAs could serve as novel prognostic biomarkers and therapeutic targets.展开更多
Long noncoding RNAs(lncRNAs)are vital regulators in tumorigenesis and metastasis.However,the pathological role of lncRNAs in hepatocellular carcinoma(HCC)is still unclear.In this study,we filtered out three lncRNAs fr...Long noncoding RNAs(lncRNAs)are vital regulators in tumorigenesis and metastasis.However,the pathological role of lncRNAs in hepatocellular carcinoma(HCC)is still unclear.In this study,we filtered out three lncRNAs from The Cancer Genome Atlas(TCGA)data that were screened for basic expression and clinical research.We selected lncRNA-NEAT1 for further study to explore its function in HCC progression and its regulatory mechanism.We identified three differentially expressed lncRNAs(DElncRNAs)in tumor and adjacent normal tissues from the TCGA library using data mining methods:lncRNA-NEAT1,lncRNA-MAGI2-AS3 and lncRNA-HCG11.Their basic expression levels were detected by qPCR.Then,we selected lncRNA-NEAT1 as a potentially important lncRNA to verity its biological function and mechanism in HCC cell lines.lncRNA-NEAT1,lncRNA-MAGI2-AS3 and lncRNA-HCG11 were overexpressed in liver cancer tissues and cell lines.We found that silencing NEAT1 in vitro can inhibit the proliferation of HuH-7 and Li-7 cells,inhibit cell migration,and induce apoptosis as well as significantly increase the level of miR-16-5p.We also confirmed that miR-16-5p has a significant correlation with Bcl-2.When NEAT1 is silenced,the expression of Bcl-2 decreases.Inhibiting miR-16-5p can restore Bcl-2 to its original level.We conclude that miR-16-5p1/lncRNA NEAT1 plays a crucial role in regulating the delivery of Bcl-2 in HCC.Overall,the miR-16-5p/lncRNA-NEAT1/Bcl-2 signaling axis may be a promising target for HCC treatment.展开更多
Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior a...Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering.The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.展开更多
The histological commitment of the lower oesophageal mucosa largely depends on a complex molecular landscape. After extended inflammatory insult due to gastroesophageal reflux disease,squamous oesophageal mucosa may d...The histological commitment of the lower oesophageal mucosa largely depends on a complex molecular landscape. After extended inflammatory insult due to gastroesophageal reflux disease,squamous oesophageal mucosa may differentiate into columnar metaplastic mucosa. In this setting,the presence of intestinal metaplasia is considered the starting point of Barrett's carcinogenetic cascade. Aside from secondary prevention strategies for Barrett's mucosa(BM) patients,there are multiple endoscopic ablative therapies available for BM eradication and for the replacement of metaplastic epithelia with a neosquamous mucosa. However,BM frequently recurs in a few years,which supports the notable phenotypic plasticity of the oesophageal mucosa. In recent years,several reports pinpointed a class of small noncoding RNAs,the micro RNAs(mi RNAs),as principal effectors and regulators of oesophageal mucosa metaplastic(and neoplastic) transformation. Because of mi RNAs notable stability in fixed archival diagnostic specimens,expression profiling of mi RNAs represent an innovative diagnostic,prognostic and predictive tool in the stratification of phenotypic alterations in the oesophageal mucosa.展开更多
At present,the function and profile of long noncoding RNAs(lncRNAs)in half-smooth tongue soles Cynoglossus semilaevis remain poorly understood.Therefore,we identified lncRNAs in the species using large-scale deep sequ...At present,the function and profile of long noncoding RNAs(lncRNAs)in half-smooth tongue soles Cynoglossus semilaevis remain poorly understood.Therefore,we identified lncRNAs in the species using large-scale deep sequencing approaches.A total of 96726222 clean reads and 2497 lncRNAs were obtained from the compound samples.In total,1694 known lncRNAs and 803 novel lncRNAs were identified.Most of the novel lncRNAs distributed mainly in a range of 200-3000 nt and contained 2-6 exons.Six novel lncRNAs were selected for expression analysis by quantitative reverse transcription-polymerase chain reaction,of which lnc_770 and lnc_150 were expressed mainly in the ovary.This study provides a valuable resource for lncRNA studies of half-smooth tongue sole and improves our understanding of the function of non-coding RNA in fish.展开更多
This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it ...This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it discusses a novel modality of epigenetic regulation,the long noncoding RNAs(lncRNAs),and provides evidence of their involvement in mesenchymal stromal/stem cells osteo-/adipogenic differentiation balance.Despite focus on lncRNAs,there is an emerging cross talk between lncRNAs and miRNAs interaction as a novel mechanism in the regulation of the function of the musculoskeletal system,by controlling bone homeostasis and bone regeneration,as well as the osteogenic differentiation of stem cells.Thus,we touched on some examples to demonstrate this interaction.In addition,we believe there is still much to discover from the effects of lncRNAs on progenitor and non-progenitor cell differentiation.We incorporated data from other published articles to review lncRNAs in normal progenitor cell osteogenic differentiation,determined lncRNAs involved in osteoarthritis pathogenesis in progenitor cells,and provided a review of lncRNAs in non-progenitor cells that are differentially regulated in osteoarthritis.In conclusion,we really enjoyed reading this article and with this information we hope to further our understanding of lncRNAs and mesenchymal stromal/stem cells regulation.展开更多
Currently,extracellular vesicles and particularly exosomes have gained a lot of research interest due to their unique roles in several biological processes.Noncoding RNAs(microRNAs,long noncoding RNAs and circular RNA...Currently,extracellular vesicles and particularly exosomes have gained a lot of research interest due to their unique roles in several biological processes.Noncoding RNAs(microRNAs,long noncoding RNAs and circular RNAs)represent a class of functional RNA with distinct regulatory roles in tumorigenesis and cancer progression.Cholangiocarcinoma is a rare but highly aggressive type of malignancy that is very challenging to diagnose,especially in early stages;surgical resection still represents the sole potentially curative treatment option.Hence,there is an urgent need for the discovery of novel diagnostic and prognostic biomarkers.Hereby,we provide a comprehensive review of the most recent discoveries that focus on exosomal noncoding RNAs in cholangiocarcinoma with the aim to identify new molecular players that could be used as biomarkers and therapeutic targets.展开更多
Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that ...Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that were once considered＂junk sequences＂or＂dark matters＂（Liu et al.,2011a;Zhang et al.,2014b）. In addition to the well-characterized housekeeping non- coding RNAs （ncRNAs） （tRNA, rRNA, small nuclear RNA and small nucleolar RNAs） and some small regulatory ncRNAs （microRNAs and small interfering RNAs）, the transcriptome of mammals could also pervasively have been transcribed long noncoding RNAs （lncRNAs, at least 200 nt） （Rinn and Chang, 2012; Xie et al., 2012）.展开更多
This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivo...This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.展开更多
Given the rapid increase of patients with autoimmune diseases and the lack of satisfactory therapies,the discovery of novel and effective therapeutic targets have been in an urgent demand.Recent studies have revealed ...Given the rapid increase of patients with autoimmune diseases and the lack of satisfactory therapies,the discovery of novel and effective therapeutic targets have been in an urgent demand.Recent studies have revealed that long noncoding RNAs(lncRNAs)play crucial roles in the development of multiple sclerosis(MS),which provides a new opportunity of uncovering novel mechanism associated with the progression of MS.This review highlights the dysregulation of lncRNAs in the development of MS in patients and animal models.Additionally,the potential clinical relevance of lncRNAs severed as therapeutic targets and diagnostic markers are discussed.展开更多
Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence...Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.展开更多
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.
基金Supported by Science and Technology Innovation Talent Project of Sichuan Province,No.2022JDRC0047the Central Government-directed Special Funds for Local Science and Technology Development Project,No.2021ZYD0085+1 种基金Natural Science Foundation of China,No.82102383Qin Chuangyuan Recruited High-level Innovation and Entrepreneurship Talents Project of Science and Technology Department of Shaanxi Province,No.QCYRCXM-2022-56.
文摘Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix.Advanced fibrosis could lead to cirrhosis and even liver cancer,which has become a significant health burden worldwide.Many studies have revealed that noncoding RNAs(ncRNAs),including microRNAs,long noncoding RNAs and circular RNAs,are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-βpathway,phosphatidylinositol 3-kinase/protein kinase B pathway,and Wnt/β-catenin pathway.NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis.NcRNAs mimics,ncRNAs in mesenchymal stem cell-derived exosomes,and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis.In this review,we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis,and discuss the potentials and challenges to use these ncRNAs for diagnosis,staging and treatment of liver fibrosis.All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.
基金supported by grants from Chinese Ministry of Science and Technology (Nos. 2011CBA01100 and 2012CB966700)the National Natural Science Foundation of China (No. 31221002)
文摘Embryonic stem cells （ESCs） hold great promises for treating and studying numerous devastating diseases. The molecular basis of their potential is not completely understood. Large noncoding RNAs （lncRNAs） are an important class of gene regulators that play essential roles in a variety of physiologic and pathologic processes. Dozens of lncRNAs are now identified to control ESC self-renewal and differentiation. Research on lncRNAs may provide novel insights into manipulating the cell fate or reprogramming somatic cells into induced pluripotent stem cells （iPSCs）. In this review, we summarize the recent research efforts in identifying functional lncRNAs and understanding how they act in ESCs, and discuss various future directions of this field.
文摘Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer （CRPC）, which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs （IncRNAs） have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding （not translated into proteins）. They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of IncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of IncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2017-I2M-2-005 and 2016-I2M-2-006Beijing Natural Science Foundation,Grant/Award Number:5171001
文摘Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.
文摘Long noncoding RNAs(lncRNAs)are important regulators of cell processes that are usually dysregulated in gastric cancer(GC).Based on their high specificity and ease of detection in tissues and body fluids,increasing attention has spurred the study of the roles of lncRNAs in GC patients.Thus,it is necessary to elucidate the molecular mechanisms and further explore the clinical applications of lncRNAs in GC.In this review,we summarize current knowledge to examine dysregulated lncRNAs in GC and their underlying molecular mechanisms and activities in GC,which involve microRNA sponging,mRNA stability,genetic variants,alternative splicing,transcription factor binding,and epigenetic modification.More significantly,the potential of lncRNAs as prognostic,circulating,and drug-resistant biomarkers for GC is also described.This review highlights the method of dissecting molecular mechanisms to explore the clinical application of lncRNAs in GC.Overall,this review offers assistance in using lncRNAs as novel candidates for molecular mechanisms and for the identification of revolutionary biomarkers for GC.
文摘Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common causeof chronic liver disorder worldwide. It represents a spectrum that includes acontinuum of different clinical entities ranging from simple steatosis to nonalcoholicsteatohepatitis, which can evolve to cirrhosis and in some cases tohepatocellular carcinoma, ultimately leading to liver failure. The pathogenesis ofNAFLD and the mechanisms underlying its progression to more pathologicalstages are not completely understood. Besides genetic factors, evidence indicatesthat epigenetic mechanisms occurring in response to environmental stimuli alsocontribute to the disease risk. Noncoding RNAs (ncRNAs), including microRNAs,long noncoding RNAs, and circular RNAs, are one of the epigenetic factors thatplay key regulatory roles in the development of NAFLD. As the field of ncRNAsis rapidly evolving, the present review aims to explore the current state ofknowledge on the roles of these RNA species in the pathogenesis of NAFLD,highlight relevant mechanisms by which some ncRNAs can modulate regulatorynetworks implicated in NAFLD, and discuss key challenges and future directionsfacing current research in the hopes of developing ncRNAs as next-generationnon-invasive diagnostics and therapies in NAFLD and subsequent progression tohepatocellular carcinoma.
基金Supported by the National Natural Science Foundation of China,No.81272762 and No.81201635the Guangdong Natural Science Funds for Distinguished Young Scholar,No.S20120011334
文摘Long non-coding RNAs(lnc RNAs), a newly discovered class of nc RNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lnc RNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lnc RNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lnc RNAs, and evaluate the p o t e n t i a l r o l e s o f l n c R N A s a s n o v e l d i a g n o s t i c biomarkers and therapeutic targets in gastrointestinal cancer.
文摘Several diverse long noncoding RNAs(lncRNAs)have been identified to be involved in hepatitis B virus(HBV)replication and oncogenesis,especially those dysregulated in HBV-related hepatocellular carcinoma(HCC).Most of these dysregulated lncRNAs are modulated by the HBV X protein.The regulatory mechanisms of some lncRNAs in HBV replication and oncogenesis have been characterized.Genetic polymorphisms of several lncRNAs affecting HBV replication or oncogenesis have also been studied.The prognosis of HCC remains poor.It is important to identify novel tumor markers for early diagnosis and find more therapeutic targets for effective treatments of HCC.Some dysregulated lncRNAs in HBV-related HCC may become biomarkers for early diagnosis and/or the therapeutic targets of HCC.This mini-review summarizes these findings briefly,focusing on recent developments.
基金Supported by National Natural Science Foundation of China,No.82170593,No.81700503the National Key Research and Development Program of China,No.2021YFC2700802.
文摘The incidence rates of hepatocellular carcinoma(HCC)have increased in recent decades.Despite advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain poor.Long noncoding RNAs(lncRNAs)and lipid metabolism play crucial roles in the development and progression of HCC.Enhanced lipid synthesis promotes HCC progression,and lncRNAs can reprogram the expression of lipogenic enzymes.Consequently,lipid metabolism-related(LMR)-lncRNAs regulate lipid anabolism,accelerating the onset and progression of HCC.This suggests that LMR-lncRNAs could serve as novel prognostic biomarkers and therapeutic targets.
基金This work was supported by(1)2019 Xing Liao Ying Cai Plan of Liaoning Province(XLYC1802049)2019 Natural Science Foundation Project of Liaoning Province(2019-ZD-0803)2020 Natural Science Foundation Project of Liaoning Province(2020-MS-297).
文摘Long noncoding RNAs(lncRNAs)are vital regulators in tumorigenesis and metastasis.However,the pathological role of lncRNAs in hepatocellular carcinoma(HCC)is still unclear.In this study,we filtered out three lncRNAs from The Cancer Genome Atlas(TCGA)data that were screened for basic expression and clinical research.We selected lncRNA-NEAT1 for further study to explore its function in HCC progression and its regulatory mechanism.We identified three differentially expressed lncRNAs(DElncRNAs)in tumor and adjacent normal tissues from the TCGA library using data mining methods:lncRNA-NEAT1,lncRNA-MAGI2-AS3 and lncRNA-HCG11.Their basic expression levels were detected by qPCR.Then,we selected lncRNA-NEAT1 as a potentially important lncRNA to verity its biological function and mechanism in HCC cell lines.lncRNA-NEAT1,lncRNA-MAGI2-AS3 and lncRNA-HCG11 were overexpressed in liver cancer tissues and cell lines.We found that silencing NEAT1 in vitro can inhibit the proliferation of HuH-7 and Li-7 cells,inhibit cell migration,and induce apoptosis as well as significantly increase the level of miR-16-5p.We also confirmed that miR-16-5p has a significant correlation with Bcl-2.When NEAT1 is silenced,the expression of Bcl-2 decreases.Inhibiting miR-16-5p can restore Bcl-2 to its original level.We conclude that miR-16-5p1/lncRNA NEAT1 plays a crucial role in regulating the delivery of Bcl-2 in HCC.Overall,the miR-16-5p/lncRNA-NEAT1/Bcl-2 signaling axis may be a promising target for HCC treatment.
基金This work was supported by the National Basic Research Program of China （973 Program, 2014CB542202）, the National HiTech Research and Development Program of China （863 Program, 2012AA020502）, the National Natural Science Foundation of China （81130080 and 31300879）, and the Key University Science Research Project of Jiangsu Province （16KJA310005）. It was also a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions （PAPD）.
文摘Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering.The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.
文摘The histological commitment of the lower oesophageal mucosa largely depends on a complex molecular landscape. After extended inflammatory insult due to gastroesophageal reflux disease,squamous oesophageal mucosa may differentiate into columnar metaplastic mucosa. In this setting,the presence of intestinal metaplasia is considered the starting point of Barrett's carcinogenetic cascade. Aside from secondary prevention strategies for Barrett's mucosa(BM) patients,there are multiple endoscopic ablative therapies available for BM eradication and for the replacement of metaplastic epithelia with a neosquamous mucosa. However,BM frequently recurs in a few years,which supports the notable phenotypic plasticity of the oesophageal mucosa. In recent years,several reports pinpointed a class of small noncoding RNAs,the micro RNAs(mi RNAs),as principal effectors and regulators of oesophageal mucosa metaplastic(and neoplastic) transformation. Because of mi RNAs notable stability in fixed archival diagnostic specimens,expression profiling of mi RNAs represent an innovative diagnostic,prognostic and predictive tool in the stratification of phenotypic alterations in the oesophageal mucosa.
基金Supported by the Shandong Provincial Natural Science Foundation(No.ZR2013CL003)the National Natural Science Foundation of China(Nos.81670398,91639102)+1 种基金the funding of Taishan Scholars of Shandong Province to Binzhou Medical Universitythe Key Research Project of Yantai City(No.2018ZHGY071)
文摘At present,the function and profile of long noncoding RNAs(lncRNAs)in half-smooth tongue soles Cynoglossus semilaevis remain poorly understood.Therefore,we identified lncRNAs in the species using large-scale deep sequencing approaches.A total of 96726222 clean reads and 2497 lncRNAs were obtained from the compound samples.In total,1694 known lncRNAs and 803 novel lncRNAs were identified.Most of the novel lncRNAs distributed mainly in a range of 200-3000 nt and contained 2-6 exons.Six novel lncRNAs were selected for expression analysis by quantitative reverse transcription-polymerase chain reaction,of which lnc_770 and lnc_150 were expressed mainly in the ovary.This study provides a valuable resource for lncRNA studies of half-smooth tongue sole and improves our understanding of the function of non-coding RNA in fish.
文摘This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it discusses a novel modality of epigenetic regulation,the long noncoding RNAs(lncRNAs),and provides evidence of their involvement in mesenchymal stromal/stem cells osteo-/adipogenic differentiation balance.Despite focus on lncRNAs,there is an emerging cross talk between lncRNAs and miRNAs interaction as a novel mechanism in the regulation of the function of the musculoskeletal system,by controlling bone homeostasis and bone regeneration,as well as the osteogenic differentiation of stem cells.Thus,we touched on some examples to demonstrate this interaction.In addition,we believe there is still much to discover from the effects of lncRNAs on progenitor and non-progenitor cell differentiation.We incorporated data from other published articles to review lncRNAs in normal progenitor cell osteogenic differentiation,determined lncRNAs involved in osteoarthritis pathogenesis in progenitor cells,and provided a review of lncRNAs in non-progenitor cells that are differentially regulated in osteoarthritis.In conclusion,we really enjoyed reading this article and with this information we hope to further our understanding of lncRNAs and mesenchymal stromal/stem cells regulation.
文摘Currently,extracellular vesicles and particularly exosomes have gained a lot of research interest due to their unique roles in several biological processes.Noncoding RNAs(microRNAs,long noncoding RNAs and circular RNAs)represent a class of functional RNA with distinct regulatory roles in tumorigenesis and cancer progression.Cholangiocarcinoma is a rare but highly aggressive type of malignancy that is very challenging to diagnose,especially in early stages;surgical resection still represents the sole potentially curative treatment option.Hence,there is an urgent need for the discovery of novel diagnostic and prognostic biomarkers.Hereby,we provide a comprehensive review of the most recent discoveries that focus on exosomal noncoding RNAs in cholangiocarcinoma with the aim to identify new molecular players that could be used as biomarkers and therapeutic targets.
基金supported by the grants from the National Key Research and Development Plan (2016YFA0100702,2016YFC0902502)the National Key Basic Research Program (973 Program) (Nos.2013CB531304 and 2011CBA01104)+1 种基金the National Sciences Foundation of China (Nos. 31301152,31670789,31671316,31370789 and 30825023)CAMS Innovation Fund for Medical Sciences (CIFMS,2016-I2M-2-001,2016-I2M-1-001,2016-I2M-1-004)
文摘Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that were once considered＂junk sequences＂or＂dark matters＂（Liu et al.,2011a;Zhang et al.,2014b）. In addition to the well-characterized housekeeping non- coding RNAs （ncRNAs） （tRNA, rRNA, small nuclear RNA and small nucleolar RNAs） and some small regulatory ncRNAs （microRNAs and small interfering RNAs）, the transcriptome of mammals could also pervasively have been transcribed long noncoding RNAs （lncRNAs, at least 200 nt） （Rinn and Chang, 2012; Xie et al., 2012）.
文摘This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.
基金supported by the National Natural Science Foundation of China(Nos.81573444,81603647 and81973221)the Natural Science Foundation of Jiangsu Province of China(No.BK20171391)+2 种基金the Special Foundation of Rheumatoid Arthritis(No.Z-2018-40)the Innovation Team of the “Double-First Class” Disciplines(No.CPU2018GF08)the Medical Science and Technology Development Foundation of Nanjing Medical University(No.2017NJMUZD055)
文摘Given the rapid increase of patients with autoimmune diseases and the lack of satisfactory therapies,the discovery of novel and effective therapeutic targets have been in an urgent demand.Recent studies have revealed that long noncoding RNAs(lncRNAs)play crucial roles in the development of multiple sclerosis(MS),which provides a new opportunity of uncovering novel mechanism associated with the progression of MS.This review highlights the dysregulation of lncRNAs in the development of MS in patients and animal models.Additionally,the potential clinical relevance of lncRNAs severed as therapeutic targets and diagnostic markers are discussed.
基金the National Natural Science Foundation of China,No.81870743 and No.81771048.
文摘Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.
