Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and ...Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.展开更多
Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer rese...Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.展开更多
Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncR...Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of m RNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.展开更多
An overwhelming majority of the transcribed genome encodes for non-coding RNA(ncR NA) sequences. Deep sequencing of the transcriptome has uncovered tens of thousands of long ncR NA(lncR NA) sequences. However, little ...An overwhelming majority of the transcribed genome encodes for non-coding RNA(ncR NA) sequences. Deep sequencing of the transcriptome has uncovered tens of thousands of long ncR NA(lncR NA) sequences. However, little is known regarding the possible functions for a vast majority of these sequences. Among those lncR NAs whose function has been experimentally validated, most serve as regulators of gene expression. LncR NAs have been found to be critical to development and homeostasis and they have been implicated in several pathologies including cancer. Here, we examine the functions and underlying mechanisms of lnc RNAs in stem cells and in cancer biology, areas linked by the actions of lncR NAs.展开更多
In China, hepatitis B virus （HBV） infection is the major cause of hepatocellular carcinoma （HCC）, which is called HBV-related HCC （HBV-HCC）, but the pathogenesis has not been clearly elu- cidated. Long non-codin...In China, hepatitis B virus （HBV） infection is the major cause of hepatocellular carcinoma （HCC）, which is called HBV-related HCC （HBV-HCC）, but the pathogenesis has not been clearly elu- cidated. Long non-coding RNAs （lncRNAs） have been paid increasing attention to, as an important regulatory molecule involved in many biological processes, as well as a variety of diseases. This study examined lncRNA that might play an important role in HBV-HCC pathogenesis by conducting lncRNA and mRNA profile comparison between HBV-HCC and normal liver tissues. The differentially ex- pressed lncRNA and mRNA profiles between HBV-HCC and normal liver tissues were analyzed by mi- croarrays. The potential protein-encoding gene regulated by lncRNA, and the biological function （gene ontology, pathway analysis） of the target gene were investigated. The results showed that the expression levels of lncRNA and mRNA in HBV-HCC tissues were different from those in normal liver tissues. As compared with normal liver tissue, 837 （4.30%） lncRNAs exhibited more than two-fold change （P〈0.05）; 325 were up-regulated, and 512 were down-regulated; 991 （5.70%） mRNAs exhibited more than 2-fold change （P〈0.05）; 733 were up-regulated and 258 were down-regulated in HBV-HCC tissue. Besides, there were 7 lncRNAs with above 10-fold elevation, 6 lncRNAs with above 10-fold decrease, 18 mRNAs with above 10-fold elevation and 11 mRNAs with above 10-fold decrease. 444 （53.05%） lncRNAs had their corresponding mRNAs, some of which were adjacent to lncRNAs. The biological analysis showed that the target gene of differentially expressed lncRNAs took part in the important bio- logical regulatory function. Target gene-related pathway analysis revealed the pathways in carcinoma and mitogen-activated protein kinase （MAPK） signaling pathways significantly changed in the HBV-HCC tissues as compared with normal liver tissues （P〈0.05）. It was suggested that as compared with normal liver tissues, the expression of lncRNAs in HBV-HCC tissues changed significantly, and lncRNAs played a key role in the pathogenesis of HBV-HCC probably by mainly regulating the carci- noma-related signaling pathway and MAPK signaling pathways.展开更多
Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multip...Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multiple genes and signalling pathways. These genetic effects can involve both protein coding genes as well as non-coding RNA genes. Long noncoding RNAs(lnc RNAs) are transcripts longer than 200 nt, constituting a subpopulation of nc RNAs. Their biological effects are not well understood comparedto small non-coding RNA(micro RNAs), but they have been recently recognized to exert a crucial role in the regulation of gene expression and modulation of signalling pathways. Notably, several studies indicated that lnc RNAs contribute to the pathogenesis and progression of HCC. Investigating the molecular mechanisms underlying lnc RNAs expression opens potential applications in diagnosis and treatment of liver disease. This editorial provides three examples(MALAT-1 metastasis associated lung adenocarcinoma transcript, HULC highly upregulated in liver cancer and HOTAIR HOX transcript antisense intergenic RNA) of well-known lnc RNAs upregulated in HCC, whose mechanisms of action are known, and for which therapeutic applications are delineated. Targeting of lnc RNAs using several approaches(siR NA-mediated silencing or changing their secondary structure) offers new possibility to treat HCC.展开更多
Gastric cancer is the second leading cause of cancer-related deaths.Metastasis,which is an important element of gastric cancer,leads to a high mortality rate and to a poor prognosis.Gastric cancer metastasis has a com...Gastric cancer is the second leading cause of cancer-related deaths.Metastasis,which is an important element of gastric cancer,leads to a high mortality rate and to a poor prognosis.Gastric cancer metastasis has a complex progression that involves multiple biological processes.The comprehensive mechanisms of metastasis remain unclear,though traditional regulation modulates the molecular functions associated with metastasis.Long non-coding RNAs(lnc RNAs) have a role in different gene regulatory pathways by epigenetic modification and by transcriptional and post-transcription regulation.lnc RNAs participate in various diseases,including Alzheimer's disease,cardiovascular disease,and cancer.The altered expressions of certain lnc RNAs are linked to gastric cancer metastasis and invasion,as with tumor suppressor genes or oncogenes.Studies have partly elucidated the roles of lnc RNAs as biomarkers and in therapies,as well as their gene regulatory mechanisms.However,comprehensive knowledge regarding the functional mechanisms of gene regulation in metastatic gastric cancer remains scarce.To provide a theoretical basis for therapeutic intervention in metastatic gastric cancer,we reviewed the functions of lnc RNAs and their regulatory roles in gastric cancer metastasis.展开更多
Long non-coding RNAs(lnc RNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lnc RNAs may play importa...Long non-coding RNAs(lnc RNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lnc RNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma(HCC). Certain lnc RNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lnc RNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lnc RNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.展开更多
Long non-coding RNAs(lncRNAs) play important roles in response to various biotic and abiotic stresses. So far, systematic identification and characterization of lncRNAs have been reported in a few model plant species ...Long non-coding RNAs(lncRNAs) play important roles in response to various biotic and abiotic stresses. So far, systematic identification and characterization of lncRNAs have been reported in a few model plant species and major crops, but their roles in abiotic stress response have not yet been reported in common wild rice(Oryza rufipogon). Dongxiang wild rice(DXWR) possesses a high degree of drought resistance and has been well recognized as a precious genetic resource for drought resistant rice breeding. We presented the reference catalog of 1 655 novel lncRNA transcripts in DXWR using strand-specific RNA sequencing and bioinformatics approaches. Meanwhile, a total of 1092 lncRNAs were determined as differentially expressed lncRNAs under drought stress. Quantitative real-time PCR results exhibited a high concordance with RNA sequencing data, which confirmed that the expression patterns of lncRNAs based on RNA sequencing were highly reliable. Furthermore, 8 711 transcripts were predicted as target genes of the differentially expressed lncRNAs. Functional annotation analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases showed that the target genes were significantly enriched in cellular and metabolic processes, cell part, binding and plant hormone signal transduction, as well as many other terms related to abiotic stress resistance. These results expanded our understanding of lncRNA biology and provided candidate regulators for genetic improvement of drought resistance in rice cultivars.展开更多
BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the ...BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the potential prognostic factors for HCC.However,the role of combined application of lncRNAs in estimating overall survival(OS)for hepatitis virus positive HCC(VHCC)is uncertain.AIM To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.METHODS The expression patterns of lncRNAs,as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database.The R package was adopted to obtain the differentially expressed lncRNAs(DElncRNAs).LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis,so as to construct a least absolute shrinkage and selection operator(LASSO)model.Subsequently,the constructed lncRNA signature was developed and validated.Afterwards,the prognostic nomogram was established,which combined the as-established lncRNA signature as well as the clinical features.Meanwhile,subgroup analysis stratified by the virus type was also performed.Finally,the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly coexpressed genes.RESULTS A total of 1420 DElncRNAs were identified,among which 406 were significant in univariate Cox regression analysis.LASSO regression confirmed 8 out of the 406 lncRNAs,including AC005722.2,AC107959.3,AL353803.1,AL589182.1,AP000844.2,AP002478.1,FLJ36000,and NPSR1-AS1.Then,the prognostic risk score was calculated.Our results displayed a significant association between the risk model and the OS of VHCC[hazard ratio=1.94,95%confidence interval(CI):1.61-2.34,log-rank P=2e-10].The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC.Furthermore,a nomogram was plotted,and the concordance index of internal validation was 0.763(95%CI:0.700-0.826).Moreover,the subgroup analysis regarding etiology confirmed this risk model.In addition,the Wnt signaling pathway,angiogenesis,the p53 pathway,and the PI3 kinase pathway were the remarkably enriched pathways.CONCLUSION An eight-lncRNA signature has been established to predict the prognosis for VHCC,which contributes to providing a novel foundation for the targeted therapy of VHCC.展开更多
Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular m...Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.展开更多
Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still n...Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still not very clear. In order to identify lncRNAs and clarify the mechanisms involved, we collected basic information and highlighted the mechanisms underlying lncRNA expression and regulation. Overall, lncRNAs are regulated by several similar transcription factors and protein-coding genes. Epigenetic modification(DNA methylation and histone modification) can also downregulate lncRNA levels in tissues and cells. Moreover, lncRNAs may be degraded or cleaved via interaction with miRNAs and miRNAassociated protein complexes. Furthermore, alternative RNA splicing(AS) may play a significant role in the post-transcriptional regulation of lncRNAs.展开更多
Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” wit...Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” with no biological functions. There are many studies conducted on lncRNAs showing they are actively involved in regulation of epigenetic, transcriptional, and post-transcriptional events. Expressions of lncRNAs are more different in many malignant tumors than in benign tumors and normal tissue. Aberration of lncRNAs is responsible to promote or suppress tumorigenesis and cancer progression. Under different circumstances, lncRNAs exhibit their roles in carcinogenesis such as MALAT1 is responsible for intervening mRNA instability, HOTAIR, MALAT1, ANRIL, PVT1 links with miRNA and histonemodifying complexes, MEG3 associates with miRNA, CCAT2, MEG3, GAS5, UCA1 allies with c-Myc or P53 causing suppression of tumor or oncogenesis. Abnormal expressions of lncRNAs are noticed in gynecological cancers, such as cervical cancer, ovarian cancer, and endometrial cancer. Identification of cervical cancer associated lncRNAs is necessary to understand the molecular biogenesis of cancers. In this review, we summarized the foundation and function of the lncRNAs in terms of tumor progression, invasion, prognosis, apoptosis, metastasis, and chemo-resistance. This review will provide references to determine the clinical applications of lncRNAs as ideal diagnostic biomarkers or therapeutic targets in cervical cancers.展开更多
基金Supported by the National Research,Development and Innovation Office,No.NVKP_16-1-2016-0004
文摘Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.
文摘Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.
文摘Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of m RNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.
文摘An overwhelming majority of the transcribed genome encodes for non-coding RNA(ncR NA) sequences. Deep sequencing of the transcriptome has uncovered tens of thousands of long ncR NA(lncR NA) sequences. However, little is known regarding the possible functions for a vast majority of these sequences. Among those lncR NAs whose function has been experimentally validated, most serve as regulators of gene expression. LncR NAs have been found to be critical to development and homeostasis and they have been implicated in several pathologies including cancer. Here, we examine the functions and underlying mechanisms of lnc RNAs in stem cells and in cancer biology, areas linked by the actions of lncR NAs.
文摘In China, hepatitis B virus （HBV） infection is the major cause of hepatocellular carcinoma （HCC）, which is called HBV-related HCC （HBV-HCC）, but the pathogenesis has not been clearly elu- cidated. Long non-coding RNAs （lncRNAs） have been paid increasing attention to, as an important regulatory molecule involved in many biological processes, as well as a variety of diseases. This study examined lncRNA that might play an important role in HBV-HCC pathogenesis by conducting lncRNA and mRNA profile comparison between HBV-HCC and normal liver tissues. The differentially ex- pressed lncRNA and mRNA profiles between HBV-HCC and normal liver tissues were analyzed by mi- croarrays. The potential protein-encoding gene regulated by lncRNA, and the biological function （gene ontology, pathway analysis） of the target gene were investigated. The results showed that the expression levels of lncRNA and mRNA in HBV-HCC tissues were different from those in normal liver tissues. As compared with normal liver tissue, 837 （4.30%） lncRNAs exhibited more than two-fold change （P〈0.05）; 325 were up-regulated, and 512 were down-regulated; 991 （5.70%） mRNAs exhibited more than 2-fold change （P〈0.05）; 733 were up-regulated and 258 were down-regulated in HBV-HCC tissue. Besides, there were 7 lncRNAs with above 10-fold elevation, 6 lncRNAs with above 10-fold decrease, 18 mRNAs with above 10-fold elevation and 11 mRNAs with above 10-fold decrease. 444 （53.05%） lncRNAs had their corresponding mRNAs, some of which were adjacent to lncRNAs. The biological analysis showed that the target gene of differentially expressed lncRNAs took part in the important bio- logical regulatory function. Target gene-related pathway analysis revealed the pathways in carcinoma and mitogen-activated protein kinase （MAPK） signaling pathways significantly changed in the HBV-HCC tissues as compared with normal liver tissues （P〈0.05）. It was suggested that as compared with normal liver tissues, the expression of lncRNAs in HBV-HCC tissues changed significantly, and lncRNAs played a key role in the pathogenesis of HBV-HCC probably by mainly regulating the carci- noma-related signaling pathway and MAPK signaling pathways.
文摘Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multiple genes and signalling pathways. These genetic effects can involve both protein coding genes as well as non-coding RNA genes. Long noncoding RNAs(lnc RNAs) are transcripts longer than 200 nt, constituting a subpopulation of nc RNAs. Their biological effects are not well understood comparedto small non-coding RNA(micro RNAs), but they have been recently recognized to exert a crucial role in the regulation of gene expression and modulation of signalling pathways. Notably, several studies indicated that lnc RNAs contribute to the pathogenesis and progression of HCC. Investigating the molecular mechanisms underlying lnc RNAs expression opens potential applications in diagnosis and treatment of liver disease. This editorial provides three examples(MALAT-1 metastasis associated lung adenocarcinoma transcript, HULC highly upregulated in liver cancer and HOTAIR HOX transcript antisense intergenic RNA) of well-known lnc RNAs upregulated in HCC, whose mechanisms of action are known, and for which therapeutic applications are delineated. Targeting of lnc RNAs using several approaches(siR NA-mediated silencing or changing their secondary structure) offers new possibility to treat HCC.
基金Grants from National Youthful Science Foundation of China,No.81101858 and No.81302147Youthful Science Foundation of Shandong Province of China,No.BS2013YY045
文摘Gastric cancer is the second leading cause of cancer-related deaths.Metastasis,which is an important element of gastric cancer,leads to a high mortality rate and to a poor prognosis.Gastric cancer metastasis has a complex progression that involves multiple biological processes.The comprehensive mechanisms of metastasis remain unclear,though traditional regulation modulates the molecular functions associated with metastasis.Long non-coding RNAs(lnc RNAs) have a role in different gene regulatory pathways by epigenetic modification and by transcriptional and post-transcription regulation.lnc RNAs participate in various diseases,including Alzheimer's disease,cardiovascular disease,and cancer.The altered expressions of certain lnc RNAs are linked to gastric cancer metastasis and invasion,as with tumor suppressor genes or oncogenes.Studies have partly elucidated the roles of lnc RNAs as biomarkers and in therapies,as well as their gene regulatory mechanisms.However,comprehensive knowledge regarding the functional mechanisms of gene regulation in metastatic gastric cancer remains scarce.To provide a theoretical basis for therapeutic intervention in metastatic gastric cancer,we reviewed the functions of lnc RNAs and their regulatory roles in gastric cancer metastasis.
文摘Long non-coding RNAs(lnc RNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lnc RNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma(HCC). Certain lnc RNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lnc RNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lnc RNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.
基金supported by the National Natural Science Foundation of China (Grant No. 31660386)the Natural Science Foundation of Jiangxi Province for Distinguished Young Scholars (Grant No. 20171BCB23040)+1 种基金the Foundation of Jiangxi Educational Committee (Grant No. GJJ170193)the Sponsored Program for Distinguished Young Scholars in Jiangxi Normal University, China
文摘Long non-coding RNAs(lncRNAs) play important roles in response to various biotic and abiotic stresses. So far, systematic identification and characterization of lncRNAs have been reported in a few model plant species and major crops, but their roles in abiotic stress response have not yet been reported in common wild rice(Oryza rufipogon). Dongxiang wild rice(DXWR) possesses a high degree of drought resistance and has been well recognized as a precious genetic resource for drought resistant rice breeding. We presented the reference catalog of 1 655 novel lncRNA transcripts in DXWR using strand-specific RNA sequencing and bioinformatics approaches. Meanwhile, a total of 1092 lncRNAs were determined as differentially expressed lncRNAs under drought stress. Quantitative real-time PCR results exhibited a high concordance with RNA sequencing data, which confirmed that the expression patterns of lncRNAs based on RNA sequencing were highly reliable. Furthermore, 8 711 transcripts were predicted as target genes of the differentially expressed lncRNAs. Functional annotation analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases showed that the target genes were significantly enriched in cellular and metabolic processes, cell part, binding and plant hormone signal transduction, as well as many other terms related to abiotic stress resistance. These results expanded our understanding of lncRNA biology and provided candidate regulators for genetic improvement of drought resistance in rice cultivars.
文摘BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the potential prognostic factors for HCC.However,the role of combined application of lncRNAs in estimating overall survival(OS)for hepatitis virus positive HCC(VHCC)is uncertain.AIM To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.METHODS The expression patterns of lncRNAs,as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database.The R package was adopted to obtain the differentially expressed lncRNAs(DElncRNAs).LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis,so as to construct a least absolute shrinkage and selection operator(LASSO)model.Subsequently,the constructed lncRNA signature was developed and validated.Afterwards,the prognostic nomogram was established,which combined the as-established lncRNA signature as well as the clinical features.Meanwhile,subgroup analysis stratified by the virus type was also performed.Finally,the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly coexpressed genes.RESULTS A total of 1420 DElncRNAs were identified,among which 406 were significant in univariate Cox regression analysis.LASSO regression confirmed 8 out of the 406 lncRNAs,including AC005722.2,AC107959.3,AL353803.1,AL589182.1,AP000844.2,AP002478.1,FLJ36000,and NPSR1-AS1.Then,the prognostic risk score was calculated.Our results displayed a significant association between the risk model and the OS of VHCC[hazard ratio=1.94,95%confidence interval(CI):1.61-2.34,log-rank P=2e-10].The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC.Furthermore,a nomogram was plotted,and the concordance index of internal validation was 0.763(95%CI:0.700-0.826).Moreover,the subgroup analysis regarding etiology confirmed this risk model.In addition,the Wnt signaling pathway,angiogenesis,the p53 pathway,and the PI3 kinase pathway were the remarkably enriched pathways.CONCLUSION An eight-lncRNA signature has been established to predict the prognosis for VHCC,which contributes to providing a novel foundation for the targeted therapy of VHCC.
基金financially supported by the National Natural Science Foundation of China,No.81371366(to HFW)Characteristic Innovation Project of Colleges and Universities in Guangdong Province of China,No.2018KTSCX075(to HFW)+3 种基金the Key Project of Social Development of Dongguan of China,No.20185071521640(to HFW)College Students’ Science and Technology Innovation Training Project,China,Nos.201810571058,GDMU2018024,GDMU2018056,GDMU2018061(to HFW)College Students’ Innovative Experimental Project in Guangdong Medical University,China,No.ZZDS001(to HFW)College Students’ Science and Technology Innovation Cultivation Project in Guangdong of China,No.pdjh2019b0217(to HFW)
文摘Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.
文摘Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still not very clear. In order to identify lncRNAs and clarify the mechanisms involved, we collected basic information and highlighted the mechanisms underlying lncRNA expression and regulation. Overall, lncRNAs are regulated by several similar transcription factors and protein-coding genes. Epigenetic modification(DNA methylation and histone modification) can also downregulate lncRNA levels in tissues and cells. Moreover, lncRNAs may be degraded or cleaved via interaction with miRNAs and miRNAassociated protein complexes. Furthermore, alternative RNA splicing(AS) may play a significant role in the post-transcriptional regulation of lncRNAs.
文摘Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” with no biological functions. There are many studies conducted on lncRNAs showing they are actively involved in regulation of epigenetic, transcriptional, and post-transcriptional events. Expressions of lncRNAs are more different in many malignant tumors than in benign tumors and normal tissue. Aberration of lncRNAs is responsible to promote or suppress tumorigenesis and cancer progression. Under different circumstances, lncRNAs exhibit their roles in carcinogenesis such as MALAT1 is responsible for intervening mRNA instability, HOTAIR, MALAT1, ANRIL, PVT1 links with miRNA and histonemodifying complexes, MEG3 associates with miRNA, CCAT2, MEG3, GAS5, UCA1 allies with c-Myc or P53 causing suppression of tumor or oncogenesis. Abnormal expressions of lncRNAs are noticed in gynecological cancers, such as cervical cancer, ovarian cancer, and endometrial cancer. Identification of cervical cancer associated lncRNAs is necessary to understand the molecular biogenesis of cancers. In this review, we summarized the foundation and function of the lncRNAs in terms of tumor progression, invasion, prognosis, apoptosis, metastasis, and chemo-resistance. This review will provide references to determine the clinical applications of lncRNAs as ideal diagnostic biomarkers or therapeutic targets in cervical cancers.
