scholarly journals Molecular Mechanisms of Long Noncoding RNAs

2011 ◽  
Vol 43 (6) ◽  
pp. 904-914 ◽  
Author(s):  
Kevin C. Wang ◽  
Howard Y. Chang
Keyword(s):  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas

scholarly journals Molecular mechanisms of long noncoding RNAs on gastric cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (8) ◽  
pp. 8601-8612 ◽  
Author(s):  
Tianwen Li ◽  
Xiaoyan Mo ◽  
Liyun Fu ◽  
Bingxiu Xiao ◽  
Junming Guo
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas

scholarly journals Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao-Xiao Li ◽  
Li-Juan Wang ◽  
Jie Hou ◽  
Hong-Yang Liu ◽  
Rui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

scholarly journals Genome-wide discovery and characterization of long noncoding RNAs in patients with multiple myeloma

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Minqiu Lu ◽  
Ying Hu ◽  
Yin Wu ◽  
Huixing Zhou ◽  
Yuan Jian ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Coiled Coil ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Aberrant Expression ◽  
Genome Wide ◽  
Wide Range ◽  
Whole Transcriptome

Abstract Background Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes in tumorigenesis. However, the role of lncRNA expression in the biology, prognosis, and molecular classification of human multiple myeloma (MM) remains unclear, especially the biological functions of the vast majority of lncRNAs. Recently, lncRNAs have been identified in neoplastic hematologic disorders. Evidence has accumulated on the molecular mechanisms of action of lncRNAs, providing insight into their functional roles in tumorigenesis. This study aimed to characterize potential lncRNAs in patients with MM. Methods In this study, the whole-transcriptome strand-specific RNA sequencing of samples from three newly diagnosed patients with MM was performed. The whole transcriptome, including lncRNAs, microRNAs, and mRNAs, was analyzed. Using these data, MM lncRNAs were systematically analyzed, and the lncRNAs involved in the occurrence of MM were identified. Results The results revealed that MM lncRNAs had distinctive characteristics different from those of other malignant tumors. Further, the functions of a set of lncRNAs preferentially expressed in MM were verified, and several lncRNAs were identified as competing endogenous RNAs. More importantly, the aberrant expression of certain lncRNAs, including maternally expressed gene3, colon cancer–associated transcript1, and coiled-coil domain-containing 26, as well as some novel lncRNAs involved in the occurrence of MM was established. Further, lncRNAs were related to some microRNAs, regulated each other, and participated in MM development. Conclusions Genome-wide screening and functional analysis enabled the identification of a set of lncRNAs involved in the occurrence of MM. The interaction exists among microRNAs and lncRNAs.

scholarly journals Long Noncoding RNAs and Messenger RNAs Expression Profiles Potentially Regulated by ZBTB7A in Nasopharyngeal Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Fei Liu ◽  
Jiazhang Wei ◽  
Yanrong Hao ◽  
Fengzhu Tang ◽  
Wei Jiao ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Differentially Expressed ◽  
Messenger Rnas ◽  
Regulatory Pathways ◽  
Different Levels

Our previous studies showed that ZBTB7A played an important role in promoting nasopharyngeal carcinoma (NPC) progression. However, molecular mechanisms of different levels of ZBTB7A are still unclear. It is necessary to search molecular markers which are closely connected with ZBTB7A. We selected NPC sublines CNE2 with stably transfecting empty plasmid (negative control, NC) and short hair RNA (shRNA) plasmid targeting ZBTB7A as research objectives. Microarray was used to screen differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) via shRNA-CNE2 versus NC-CNE2. Quantitative PCR (qPCR) was used to validate lncRNAs and mRNAs from the sublines, chronic rhinitis, and NPC tissues. Bioinformatics was used to analyze regulatory pathways which were connected with ZBTB7A. The 1501 lncRNAs (long noncoding RNAs) and 1275 differentially expressed mRNAs were upregulated or downregulated over 2-fold. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the upregulated or downregulated carbohydrate and lipid metabolisms probably involved in carcinogenicity of shRNA-CNE2 (P-value cut-off was 0.05). In order to find the molecular mechanisms of ZBTB7A, we validated 12 differentially expressed lncRNAs and their nearby mRNAs by qPCR. Most of the differentially expressed mRNAs are closely connected with carbohydrate and lipid metabolisms in multiply cancers. Furthermore, part of them were validated in NPC and rhinitis tissues by qPCR. As a result, NR_047538, ENST00000442852, and fatty acid synthase (FASN) were closely associated with NPC. ZBTB7A had a positive association with NR_047538 and negative associations with ENST00000442852 and FASN. The results probably provide novel candidate biomarkers for NPC progression with different levels of ZBTB7A.

scholarly journals Identification of Differentially Expressed Genes and Long Noncoding RNAs Associated with Parkinson’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Lu-Mei Chi ◽  
Li-Ping Wang ◽  
Dan Jiao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Gene Expression Omnibus ◽  
Long Noncoding Rnas ◽  
Differentially Expressed ◽  
Similar Treatment ◽  
Blood Samples

Objectives. This study aims to determine differentially expressed genes (DEGs) and long noncoding RNAs (lncRNAs) associated with Parkinson’s disease (PD) using a microarray. Methods. We downloaded the microarray data GSE6613 from the Gene Expression Omnibus, which included 105 samples. We selected 72 samples comprising 22 healthy control blood samples and 50 PD blood samples for further analysis. Later, we used Limma to screen DEGs and differentially expressed lncRNAs (DElncRNAs) and estimated their functions by the Gene Ontology (GO). Besides, the competing endogenous RNA (ceRNA) network, including microRNAs, lncRNAs, and mRNAs, was constructed to elucidate the regulatory mechanism. Furthermore, we performed the KEGG pathway enrichment with mRNAs in the ceRNA regulatory network and constructed a final network, including pathways, mRNAs, microRNAs, and lncRNAs. Results. Overall, we obtained 394 DEGs, including 207 upregulated DEGs and 187 downregulated DEGs, and 7 DElncRNAs, including 2 upregulated DElncRNAs and 5 downregulated DElncRNAs. Insulin-like growth factor-1 receptor (IGF1R) was considerably enriched in the endocytosis pathway. In the ceRNA regulation network, IGF1R was the target of hsa-miR-133b and lncRNAs of XIST, and PART1 could also be the target of hsa-miR-133b. While the upregulated DEGs were enriched in the GO terms of the cytoskeleton, cytoskeletal part, and microtubule cytoskeleton, the downregulated DEGs were enriched in the immune response. PRKACA was markedly enriched in numerous pathways, including the MAPK and insulin signaling pathways. Conclusions. IGF1R, PRKACA, and lncRNA-XIST could be potentially involved in PD, and these diverse molecular mechanisms could support the development of the similar treatment for PD.

Role of Long Coding RNAs in Epigenetic Modulation of Hematopoiesis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-28-SCI-28
Author(s):  
Mitchell J. Weiss
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Fetal Liver ◽  
Protein Localization ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Similar Degree ◽  
Erythroid Progenitors

Abstract Long noncoding (Lnc) RNAs are RNA transcripts greater than 200 nucleotides (nt) that regulate gene expression independent of protein coding potential (1-3). It is estimated that thousands of lncRNAs play vital roles in diverse cellular processes. LncRNAs modulate many stages of gene expression by regulating transcription, epigenetics, splicing, translation, and protein localization. We hypothesize that multiple lncRNAs are expressed specifically during erythrocyte and megakaryocyte differentiation, and are likely to have important roles. To identify lncRNAs in erythro-megakaryopoiesis, we performed strand-specific, paired-end deep sequencing (RNA-Seq) to a depth of 200 million reads per sample on two replicates each of murine Ter119+erythroblasts, CD41+ megakaryocytes and bipotential megakaryocyte-erythroid progenitors (MEPs) [lin- Kit+ Sca1- CD16/32- CD34-], and used bioinformatic filtering tools to identify approximately 1,100 candidate lncRNAs. Over 60 percent of these lncRNAs are novel unannotated transcripts with exquisite lineage-specific expression. Using erythroid and megakaryocytic primary cell ChIP-Seq for key transcription factors (TFs) GATA1, TAL1, GATA2,and FLI1, we found that the loci of lncRNAs show similar degree of TF binding as coding genes. We used the erythroid line G1E-ER4 (which expresses estrogen-activated GATA1) to confirm that lncRNAs bound by GATA1 are also directly regulated by it. Furthermore, we used histone methylation ChIP-Seq to show that most lncRNAs arise from classical “promoters” with high H3K4me3 levels and low H3K4me1 levels. Thus, we find that lncRNAs show epigenetic features similar to the promoters of coding genes and are directly regulated by similar TF networks. Comparison of the transcriptomes of mouse fetal liver and human cord blood erythroblasts demonstrated that lncRNAs are expressed in a highly species-specific fashion, i.e., most lncRNAs identifiable in one species are not transcribed in the other, even though the corresponding genomic region is present in both species. Numerous non-conserved but functional lncRNAs are reported in the literature, and the significance of conservation in lncRNA biology is greatly debated. In order to identify functional lncRNAs, we are currently performing RNAi knockdown on numerous candidates to assess how loss of function affects erythroid maturation. We are also performing HITS-CLIP of key chromatin modifying complexes and erythroid transcription factors to identify lncRNAs bound to them. Our studies are beginning to define new layers of gene regulation in normal erythro-megakaryopoiesis, which may be relevant to the pathophysiology of related disorders including various anemias, myeloproliferative and myelodysplastic syndromes and leukemias. 1. Wang K.C., Chang H.Y. Molecular mechanisms of long noncoding RNAs. Molecular Cell. 2011;43(6):904-914. Prepublished on 2011/09/20 as DOI 10.1016/j.molcel.2011.08.018. 2. Hu W., Alvarez-Dominguez J.R., Lodish H.F. Regulation of mammalian cell differentiation by long non-coding RNAs. EMBO reports. 2012;13(11):971-983. Prepublished on 2012/10/17 as DOI 10.1038/embor.2012.145. 3. Paralkar V.R., Weiss M.J. Long noncoding RNAs in biology and hematopoiesis. Blood. 2013;121(24):4842-4846. Prepublished on 2013/05/07 as DOI 10.1182/blood-2013-03-456111. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Transcriptome Analysis of Long Noncoding RNAs in Toll-Like Receptor 3-Activated Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Shihua Wang ◽  
Xiaoxia Li ◽  
Robert Chunhua Zhao
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Length Distribution ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Differentially Expressed ◽  
Therapeutic Effects ◽  
Wide Range

Mesenchymal stem cells (MSCs) possess great immunomodulatory capacity which lays the foundation for their therapeutic effects in a variety of diseases. Recently, toll-like receptors (TLR) have been shown to modulate MSC functions; however, the underlying molecular mechanisms are poorly understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are an important class of regulators involved in a wide range of biological processes. To explore the potential involvement of lncRNAs in TLR stimulated MSCs, we performed a comprehensive lncRNA and mRNA profiling through microarray. 10.2% of lncRNAs (1733 out of 16967) and 15.1% of mRNA transcripts (1760 out of 11632) were significantly differentially expressed (absolute fold-change≥5 ,Pvalue≤0.05) in TLR3 stimulated MSCs. Furthermore, we characterized the differentially expressed lncRNAs through their classes and length distribution and correlated them with differentially expressed mRNA. Here, we are the first to determine genome-wide lncRNAs expression patterns in TLR3 stimulated MSCs by microarray and this work could provide a comprehensive framework of the transcriptome landscapes of TLR3 stimulated MSCs.

scholarly journals Long Noncoding RNAs as a Key Player in Hepatocellular Carcinoma

2017 ◽  
Vol 9 ◽  
pp. 1179299X1773730 ◽  
Author(s):  
Mrigaya Mehra ◽  
Ranjit Chauhan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Structural Integrity ◽  
Gene Expression Regulation ◽  
Noncoding Rnas ◽  
Clinical Applications ◽  
Long Noncoding Rnas ◽  
Protein Coding ◽  
Cellular Processes ◽  
The World

Hepatocellular carcinoma (HCC) is a major malignancy in the liver and has emerged as one of the main cancers in the world with a high mortality rate. However, the molecular mechanisms of HCC are still poorly understood. Long noncoding RNAs (lncRNAs) have recently come to the forefront as functional non–protein-coding RNAs that are involved in a variety of cellular processes ranging from maintaining the structural integrity of chromosomes to gene expression regulation in a spatiotemporal manner. Many recent studies have reported the involvement of lncRNAs in HCC which has led to a better understanding of the underlying molecular mechanisms operating in HCC. Long noncoding RNAs have been shown to regulate development and progression of HCC, and thus, lncRNAs have both diagnostic and therapeutic potentials. In this review, we present an overview of the lncRNAs involved in different stages of HCC and their potential in clinical applications which have been studied so far.

scholarly journals PVT1: A Rising Star among Oncogenic Long Noncoding RNAs

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Teresa Colombo ◽  
Lorenzo Farina ◽  
Giuseppe Macino ◽  
Paola Paci
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Competing Endogenous Rna ◽  
Protein Coding ◽  
Myc Oncogene ◽  
Non Coding Rnas

It is becoming increasingly clear that short and long noncoding RNAs critically participate in the regulation of cell growth, differentiation, and (mis)function. However, while the functional characterization of short non-coding RNAs has been reaching maturity, there is still a paucity of well characterized long noncoding RNAs, even though large studies in recent years are rapidly increasing the number of annotated ones. The long noncoding RNA PVT1 is encoded by a gene that has been long known since it resides in the well-known cancer risk region 8q24. However, a couple of accidental concurrent conditions have slowed down the study of this gene, that is, a preconception on the primacy of the protein-coding over noncoding RNAs and the prevalent interest in its neighbor MYC oncogene. Recent studies have brought PVT1 under the spotlight suggesting interesting models of functioning, such as competing endogenous RNA activity and regulation of protein stability of important oncogenes, primarily of the MYC oncogene. Despite some advancements in modelling the PVT1 role in cancer, there are many questions that remain unanswered concerning the precise molecular mechanisms underlying its functioning.

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