Dataset Information

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion.

ABSTRACT: Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into "networks" based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer.Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.

SUBMITTER: Song YX

PROVIDER: S-EPMC5561086 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion.

Song Yong-Xi YX Sun Jing-Xu JX Zhao Jun-Hua JH Yang Yu-Chong YC Shi Jin-Xin JX Wu Zhong-Hua ZH Chen Xiao-Wan XW Gao Peng P Miao Zhi-Feng ZF Wang Zhen-Ning ZN

Nature communications 20170818 1

Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into "networks" based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 an ...[more]

PMID: 28819095

Similar Datasets

Project description:BackgroundCurrently, cancer-related competing endogenous RNA (ceRNA) networks are attracting significant interest. As long noncoding RNA ZEB1-AS1 has been reported to function as an oncogene due to sponging microRNAs (miRNAs) in several cancers, we hypothesized that it could interact with specific miRNAs to form regulatory networks and facilitate the growth of gastric cancer (GC).MethodsMiRNAs interacting with ZEB1-AS1 were screened for and selected by bioinformatics analysis. Overexpression or repression of ZEB1-AS1 was performed to determine whether it could regulate selected miRNAs. Quantitative real-time polymerase chain reactions (qPCR) validated the expression profiles of ZEB1-AS1 and miR-149-3p in GC cell lines and tissue. Statistical analysis determined the clinical significance of ZEB1-AS1 in relation to miR-149-3p. Cell counting, wound healing and transwell assays were performed to assess cell proliferation, migration and invasion. A luciferase reporter assay was utilized to confirm the putative miR-149-3p-binding sites in ZEB1-AS1.ResultsBriefly, bioinformatics analysis inferred that ZEB1-AS1 interacts with miR-204, miR-610, and miR-149. Gain- or loss-of function assays suggested that ZEB1-AS1 negatively regulates miR-149-3p, miR-204-5p and miR-610 in GC cells. Validated by qPCR, ZEB1-AS1 was up-regulated and miR-149-3p down-regulated in GC cells and tissue. Data analyses indicated that ZEB1-AS1 and miR-149-3p are associated with the independent diagnosis and prognosis of GC. Functional assays support the theory that miR-149-3p hinders GC proliferation, migration and invasion, whereas its overexpression abrogates the corresponding effects induced by ZEB1-AS1. Lastly, dissection of the molecular mechanisms involved indicated that ZEB1-AS1 can regulate GC partly via a ZEB1-AS1/miR-149-3p axis.ConclusionsZEB1-AS1 can interact with specific miRNAs, forming a miRNA-mediated ceRNA network and promoting GC progress, partly through a ZEB1-AS1/miR-149-3p axis.

Project description:Long non-coding RNAs (lncRNAs) are ncRNA transcripts >200 nucleotides that are important genetic regulators. LncRNAs can directly regulate mRNA through a lncRNA-mRNA regulatory mode and can also regulate mRNA through competitive binding to micro (mi)RNA, which is generally known as the competitive endogenous RNA (ceRNA) network. The present study evaluated the functional roles and regulatory networks of lncRNAs in chronic glomerulonephritis (CGN). The proliferative ability of mouse glomerular mesangial cells (GMCs) induced by different concentrations of lipopolysaccharide (LPS) was assessed using the Cell Counting Kit-8 assay, and RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs in LPS-induced GMCs. Based on the sequencing results, six lncRNAs were selected for validation using reverse transcription-quantitative PCR (RT-qPCR). Furthermore, the lncRNA-mRNA regulatory network and the lncRNA-miRNA-mRNA ceRNA network were constructed to assess the role and mechanism of CGN-related lncRNAs. To elucidate the biological functions of lncRNAs, Gene Ontology (GO) biological process term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on all mRNAs involved in the lncRNA-mRNA regulatory network and in the ceRNA network. A total of 1,532 differentially expressed lncRNAs, including 594 upregulated lncRNAs and 938 downregulated lncRNAs, were identified using RNA-seq. The results of RT-qPCR validation were consistent with RNA-seq results. An lncRNA-mRNA regulatory network, including 236 lncRNAs and 556 mRNAs, and a ceRNA network, including 6 lncRNAs, 18 miRNAs and 419 mRNAs, were successfully constructed. The GO biological process term enrichment and KEGG pathway enrichment analyses demonstrated that those lncRNAs were often related to inflammatory response and substance metabolism. The present study identified key CGN-related lncRNAs in LPS-induced GMCs, and further demonstrated a global view of the lncRNA-mRNA regulatory network and ceRNA network involved in CGN. These results offered novel insights into the roles of lncRNAs in the pathogenesis of CGN and identified potential diagnostic biomarkers.

Project description:Long non‑coding RNAs (lncRNAs) play critical roles in the development and progression of cancers. The present study aimed to identify novel lncRNAs and associated microRNAs (miRNAs or miRs) and mRNAs in gastric cancer. Differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) of 6 paired gastric cancer and normal tissues were identified using microarray. The DEmiRNAs between gastric cancer and the normal control tissues were identified using miRNA‑seq data from Cancer Genome Atlas. Common DElncRNAs from the Cancer RNA‑Seq Nexus database and circlncRNAnet database were analyzed. A DElncRNAs‑DEmiRNAs‑DEmRNAs network was constructed by target prediction. Functional enrichment analysis was employed to predict the function of DEmRNAs in the network. The correlation between the expression of DElncRNAS and DEmRNAs in the network was analyzed. The expression levels of several genes were validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). A total of 1,297 DElncRNAs, 2,037 DEmRNAs and 171 DEmiRNAs were identified. Among the 4 lncRNAs common to the 3 datasets, prostate androgen‑regulated transcript 1 (PART1) was selected for further analysis. The analysis identified 5 DEmiRNAs and 13 DEmRNAs in the PART1‑mediated ceRNA network. The DEmRNAs in the ceRNA network were markedly enriched in cancer‑related biological processes (response to hypoxia, positive regulation of angiogenesis and positive regulation of endothelial cell proliferation) and pathways (cGMP‑PKG signaling pathway, cAMP signaling pathway and proteoglycans in cancer). Out of the 13 DEmRNAs, 11 were positively associated with PART1. The downregulation of PART1, myosin light chain 9 (MYL9), potassium calcium‑activated channel subfamily M alpha 1 (KCNMA1), cholinergic receptor muscarinic 1 (CHRM1), solute carrier family 25 member 4 (SLC25A4) and ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2) expression levels in gastric cancer was validated by RT‑qPCR. On the whole, the current study identified a novel lncRNA and associated miRNAs and mRNAs that are involved in the pathogenesis of gastric cancer that may serve as potential therapeutic targets for the treatment of gastric cancer.

Dataset Information

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion.

Publications

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets