Dataset Information

Identification and development of long non-coding RNA-associated regulatory network in colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the leading causes of cancer-associated death globally. Long non-coding RNAs (lncRNAs) have been identified as micro RNA (miRNA) sponges in a competing endogenous RNA (ceRNA) network and are involved in the regulation of mRNA expression. This study aims to construct a lncRNA-associated ceRNA network and investigate the prognostic biomarkers in CRC. A total of 38 differentially expressed (DE) lncRNAs, 23 DEmiRNAs and 27 DEmRNAs were identified by analysing the expression profiles of CRC obtained from The Cancer Genome Atlas (TCGA). These RNAs were chosen to develop a ceRNA regulatory network of CRC, which comprised 125 edges. Survival analysis showed that four lncRNAs, six miRNAs and five mRNAs were significantly associated with overall survival. A potential regulatory axis of ADAMTS9-AS2/miR-32/PHLPP2 was identified from the network. Experimental validation was performed using clinical samples by quantitative real-time PCR (qRT-PCR), which showed that expression of the genes in the axis was associated with clinicopathological features and the correlation among them perfectly conformed to the 'ceRNA theory'. Overexpression of ADAMTS9-AS2 in colon cancer cell lines significantly inhibited the miR-32 expression and promoted PHLPP2 expression, while ADAMTS9-AS2 knockdown had the opposite effects. The constructed novel ceRNA network may provide a comprehensive understanding of the mechanisms of CRC carcinogenesis. The ADAMTS9-AS2/miR-32/PHLPP2 regulatory axis may serve as a potential therapeutic target for CRC.

SUBMITTER: Pan H

PROVIDER: S-EPMC6653593 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Identification and development of long non-coding RNA-associated regulatory network in colorectal cancer.

Pan Hongda H Pan Jingxin J Song Shibo S Ji Lei L Lv Hong H Yang Zhangru Z

Journal of cellular and molecular medicine 20190529 8

Colorectal cancer (CRC) is one of the leading causes of cancer-associated death globally. Long non-coding RNAs (lncRNAs) have been identified as micro RNA (miRNA) sponges in a competing endogenous RNA (ceRNA) network and are involved in the regulation of mRNA expression. This study aims to construct a lncRNA-associated ceRNA network and investigate the prognostic biomarkers in CRC. A total of 38 differentially expressed (DE) lncRNAs, 23 DEmiRNAs and 27 DEmRNAs were identified by analysing the ex ...[more]

PMID: 31144439

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Project description:Background:The aim of this study was to investigate the regulatory network of lncRNAs as competing endogenous RNAs (ceRNA) in bladder urothelial carcinoma (BUC) based on gene expression data derived from The Cancer Genome Atlas (TCGA). Materials and methods:RNA sequence profiles and clinical information from 414 BUC tissues and 19 non-tumor adjacent tissues were downloaded from TCGA. Differentially expressed RNAs derived from BUC and non-tumor adjacent samples were identified using the R package "edgeR". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using the "clusterProfiler" package. Gene ontology and protein-protein interaction (PPI) networks were analyzed for the differentially expressed mRNAs using the "STRING" database. The network for the dysregulated lncRNA associated ceRNAs was then constructed for BUC using miRcode, miRTarBase, miRDB, and TargetScan. Cox regression analysis was performed to identify independent prognostic RNAs associated with BUC overall survival (OS). Survival analysis for the independent prognostic RNAs within the ceRNA network was calculated using Kaplan-Meier curves. Results:Based on our analysis, a total of 666, 1819 and 157 differentially expressed lncRNAs, mRNAs and miRNAs were identified respectively. The ceRNA network was then constructed and contained 59 lncRNAs, 23 DEmiRNAs, and 52 DEmRNAs. In total, 5 lncRNAs (HCG22, ADAMTS9-AS1, ADAMTS9-AS2, AC078778.1, and AC112721.1), 2 miRNAs (hsa-mir-145 and hsa-mir-141) and 6 mRNAs (ZEB1, TMEM100, MAP1B, DUSP2, JUN, and AIFM3) were found to be related to OS. Two lncRNAs (ADAMTS9-AS1 and ADAMTS9-AS2) and 4 mRNA (DUSP2, JUN, MAP1B, and TMEM100) were validated using GEPIA. Thirty key hub genes were identified using the ranking method of degree. KEGG analysis demonstrated that the majority of the DEmRNAs were involved in pathways associated with cancer. Conclusion:Our findings provide an understanding of the important role of lncRNA-related ceRNAs in BUC. Additional experimental and clinical validations are required to support our findings.

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Project description:Schizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein-protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.

Dataset Information

Identification and development of long non-coding RNA-associated regulatory network in colorectal cancer.

Publications

Identification and development of long non-coding RNA-associated regulatory network in colorectal cancer.

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