Background:Hepatic ischemia-reperfusion injury(HIRI)is a common complication of liver surgeries,such as hepatectomy and liver transplantation.In recent years,several non-coding RNAs(nc RNAs)including long non-coding R...Background:Hepatic ischemia-reperfusion injury(HIRI)is a common complication of liver surgeries,such as hepatectomy and liver transplantation.In recent years,several non-coding RNAs(nc RNAs)including long non-coding RNAs(lnc RNAs)and micro RNAs(mi RNAs)have been identified as factors involved in the pathological progression of HIRI.In this review,we summarized the latest research on lnc RNAs,mi RNAs and the lnc RNA-mi RNA regulatory networks in HIRI.Data sources:The Pub Med and Web of Science databases were searched for articles published up to December 2021 using the following keywords:“hepatic ischemia-reperfusion injury”,“lnc RNA”,“long noncoding RNA”,“mi RNA”and“micro RNA”.The bibliography of the selected articles was manually screened to identify additional studies.Results:The mechanism of HIRI is complex,and involves multiple lnc RNAs and mi RNAs.The roles of lnc RNAs such as AK139328,CCAT1,MALAT1,TUG1 and NEAT1 have been established in HIRI.In addition,numerous mi RNAs are associated with apoptosis,autophagy,oxidative stress and cellular inflammation that accompany HIRI pathogenesis.Based on the literature,we conclude that four lnc RNA-mi RNA regulatory networks mediate the pathological progression of HIRI.Furthermore,the expression levels of some lnc RNAs and mi RNAs undergo significant changes during the progression of HIRI,and thus are potential prognostic markers and therapeutic targets.Conclusions:Complex lnc RNA-mi RNA-m RNA networks regulate HIRI progression through mutual activation and antagonism.It is necessary to screen for more HIRI-associated lnc RNAs and mi RNAs in order to identify novel therapeutic targets.展开更多
Background:Follicular atresia has been shown to be strongly associated with a low follicle utilization rate and female infertility,which are regulated by many factors such as microRNAs(miRNAs),which constitute a class...Background:Follicular atresia has been shown to be strongly associated with a low follicle utilization rate and female infertility,which are regulated by many factors such as microRNAs(miRNAs),which constitute a class of noncoding RNAs(ncRNAs).However,little is known about long noncoding RNAs(lncRNAs),which constitute another ncRNA family that regulate follicular atresia.Results:A total of 77 differentially expressed lncRNAs,including 67 upregulated and 10 downregulated lncRNAs,were identified in early atretic follicles compared to healthy follicles by RNA-Sequencing.We characterized a noncoding RNA that was highly expressed in atretic follicles(NORHA).As an intergenic lncRNA,NORHA was one of the upregulated lncRNAs identified in the atretic follicles.To determine NORHA function,RT-PCR,flow cytometry and western blotting were performed,and the results showed that NORHA was involved in follicular atresia by influencing GC apoptosis with or without oxidative stress.To determine the mechanism of action,bioinformatics analysis,luciferase reporter assay and RNA immunoprecipitation assay were performed,and the results showed that NORHA acted as a‘sponge’,that directly bound to the miR-183-96-182 cluster,and thus prevented its targeted inhibition of FoxO1,a major sensor and effector of oxidative stress.Conclusions:We provide a comprehensive perspective of lncRNA regulation of follicular atresia,and demonstrate that NORHA,a novel lncRNA related to follicular atresia,induces GC apoptosis by influencing the activities of the miR-183-96-182 cluster and FoxO1 axis.展开更多
ncRNAs have been identified as potential regulatory molecules and have multiple biological roles. Aberrant expression of specific ncRNAs contributes to multiple biological processes and many human diseases. Herein, we...ncRNAs have been identified as potential regulatory molecules and have multiple biological roles. Aberrant expression of specific ncRNAs contributes to multiple biological processes and many human diseases. Herein, we simultaneously profiled miRNA, lncRNA and mRNA in human HepG2 and L02 cells applying high-throughput sequencing and micro-array technologies. Abnormal miRNA, lncRNA and mRNA profiles were assessed through fold change filtering. A cross-platform integrated analysis method was developed to analyze differentially expressed miRNA, lncRNA and mRNA profiles. miRNA-mRNA interaction was analyzed according to their functional relationships. Target mRNAs of aberrantly expressed miRNAs were obtained from experimentally validated datasets or predicted using some programs. Generally, multiple target mRNAs were involved, and they have versatile roles by functional enrichment analysis. Ac-cording to actual expression datasets in the study, compared to deregulated miRNAs, these theoretical target mRNAs showed various expression patterns. The consistent or inconsistent expression was mainly derived from complex, mul-tiple, flexible and alternative regulatory relationships between miRNA and mRNA. Further, miRNA/mRNA and lncRNA were completely surveyed based on their location distributions on human chromosomes. Many miRNA-lncRNA and mRNA-lncRNA pairs always were located on the same strand or different strands in the specific genomic region. Due to the location distributions, they might have partly or completely overlapped regions or they could be reverse complementarily binding. These miRNA/mRNA-lncRNA pairs showed consistent or inconsistent expression pat-terns, although they might have functional relationships through reverse complementarily binding events. Moreover, we also detected and analyzed various isomiRs from a given miRNA locus, including those isomiRs with 3’ additional non-template nucleotides. These isomiRs, especially for those 5’ isomiRs with the new “seed sequences” through “seed shifting” events, maybe have potential biological roles as well as isomiR repertoire and their expression patterns. The integrative analysis provides potential functional relationships between miRNA, lncRNA and mRNA across different datasets. The complex and various expression patterns suggest a robust regulatory network across different regulatory molecules and their targets.展开更多
基金supported by grants from the National Natural Sciences Foundation of China(81974442)Guangzhou Health Science and technology project(20202A011010)。
文摘Background:Hepatic ischemia-reperfusion injury(HIRI)is a common complication of liver surgeries,such as hepatectomy and liver transplantation.In recent years,several non-coding RNAs(nc RNAs)including long non-coding RNAs(lnc RNAs)and micro RNAs(mi RNAs)have been identified as factors involved in the pathological progression of HIRI.In this review,we summarized the latest research on lnc RNAs,mi RNAs and the lnc RNA-mi RNA regulatory networks in HIRI.Data sources:The Pub Med and Web of Science databases were searched for articles published up to December 2021 using the following keywords:“hepatic ischemia-reperfusion injury”,“lnc RNA”,“long noncoding RNA”,“mi RNA”and“micro RNA”.The bibliography of the selected articles was manually screened to identify additional studies.Results:The mechanism of HIRI is complex,and involves multiple lnc RNAs and mi RNAs.The roles of lnc RNAs such as AK139328,CCAT1,MALAT1,TUG1 and NEAT1 have been established in HIRI.In addition,numerous mi RNAs are associated with apoptosis,autophagy,oxidative stress and cellular inflammation that accompany HIRI pathogenesis.Based on the literature,we conclude that four lnc RNA-mi RNA regulatory networks mediate the pathological progression of HIRI.Furthermore,the expression levels of some lnc RNAs and mi RNAs undergo significant changes during the progression of HIRI,and thus are potential prognostic markers and therapeutic targets.Conclusions:Complex lnc RNA-mi RNA-m RNA networks regulate HIRI progression through mutual activation and antagonism.It is necessary to screen for more HIRI-associated lnc RNAs and mi RNAs in order to identify novel therapeutic targets.
基金This work was supported by the National Natural Science Foundation of China(32072693 and 31630072)the Qing Lan Project of Jiangsu Province(2020).
文摘Background:Follicular atresia has been shown to be strongly associated with a low follicle utilization rate and female infertility,which are regulated by many factors such as microRNAs(miRNAs),which constitute a class of noncoding RNAs(ncRNAs).However,little is known about long noncoding RNAs(lncRNAs),which constitute another ncRNA family that regulate follicular atresia.Results:A total of 77 differentially expressed lncRNAs,including 67 upregulated and 10 downregulated lncRNAs,were identified in early atretic follicles compared to healthy follicles by RNA-Sequencing.We characterized a noncoding RNA that was highly expressed in atretic follicles(NORHA).As an intergenic lncRNA,NORHA was one of the upregulated lncRNAs identified in the atretic follicles.To determine NORHA function,RT-PCR,flow cytometry and western blotting were performed,and the results showed that NORHA was involved in follicular atresia by influencing GC apoptosis with or without oxidative stress.To determine the mechanism of action,bioinformatics analysis,luciferase reporter assay and RNA immunoprecipitation assay were performed,and the results showed that NORHA acted as a‘sponge’,that directly bound to the miR-183-96-182 cluster,and thus prevented its targeted inhibition of FoxO1,a major sensor and effector of oxidative stress.Conclusions:We provide a comprehensive perspective of lncRNA regulation of follicular atresia,and demonstrate that NORHA,a novel lncRNA related to follicular atresia,induces GC apoptosis by influencing the activities of the miR-183-96-182 cluster and FoxO1 axis.
文摘ncRNAs have been identified as potential regulatory molecules and have multiple biological roles. Aberrant expression of specific ncRNAs contributes to multiple biological processes and many human diseases. Herein, we simultaneously profiled miRNA, lncRNA and mRNA in human HepG2 and L02 cells applying high-throughput sequencing and micro-array technologies. Abnormal miRNA, lncRNA and mRNA profiles were assessed through fold change filtering. A cross-platform integrated analysis method was developed to analyze differentially expressed miRNA, lncRNA and mRNA profiles. miRNA-mRNA interaction was analyzed according to their functional relationships. Target mRNAs of aberrantly expressed miRNAs were obtained from experimentally validated datasets or predicted using some programs. Generally, multiple target mRNAs were involved, and they have versatile roles by functional enrichment analysis. Ac-cording to actual expression datasets in the study, compared to deregulated miRNAs, these theoretical target mRNAs showed various expression patterns. The consistent or inconsistent expression was mainly derived from complex, mul-tiple, flexible and alternative regulatory relationships between miRNA and mRNA. Further, miRNA/mRNA and lncRNA were completely surveyed based on their location distributions on human chromosomes. Many miRNA-lncRNA and mRNA-lncRNA pairs always were located on the same strand or different strands in the specific genomic region. Due to the location distributions, they might have partly or completely overlapped regions or they could be reverse complementarily binding. These miRNA/mRNA-lncRNA pairs showed consistent or inconsistent expression pat-terns, although they might have functional relationships through reverse complementarily binding events. Moreover, we also detected and analyzed various isomiRs from a given miRNA locus, including those isomiRs with 3’ additional non-template nucleotides. These isomiRs, especially for those 5’ isomiRs with the new “seed sequences” through “seed shifting” events, maybe have potential biological roles as well as isomiR repertoire and their expression patterns. The integrative analysis provides potential functional relationships between miRNA, lncRNA and mRNA across different datasets. The complex and various expression patterns suggest a robust regulatory network across different regulatory molecules and their targets.