Dataset Information

LncRNA MAGI2-AS3 Prevents the Development of HCC via Recruiting KDM1A and Promoting H3K4me2 Demethylation of the RACGAP1 Promoter.

ABSTRACT: Accumulating studies have implicated the role of long non-coding RNAs (lncRNAs) in the pathogenesis of hepatocellular carcinoma (HCC) through the regulating transcription and mRNA stability. A recent report has linked Rac GTPase-activating protein 1 (RACGAP1) to the early recurrence of HCC. The current study aimed to ascertain whether MAGI2 antisense RNA 3 (MAGI2-AS3) influences the development of HCC by regulating RACGAP1. MAGI2-AS3 expression was initially quantified in both the HCC tissues and cell lines. In order to elucidate the role of MAGI2-AS3 in the development of HCC, MAGI2-AS3 was overexpressed or silenced in HCC cells after which cell proliferation, apoptosis, invasion, and migration were evaluated. Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and biotin-labeled RNA pull-down assays were conducted to determine the interactions among MAGI2-AS3, KDM1A, and RACGAP1. Finally, the effects of MAGI2-AS3 and RACGAP1 on the tumorigenesis of transplanted HCC cells in nude mice were evaluated. MAGI2-AS3 was found to be under-expressed in HCC tissues and cell lines. The restoration of MAGI2-AS3 was identified to markedly inhibit HCC cell growth, migrating ability, and invasiveness, and promote cell apoptosis. Interaction between MAGI2-AS3 and KDM1A was identified. KDM1A recruited by MAGI2-AS3 was found to promote H3K4me2 demethylation at the RACGAP1 promoter, which ultimately decreased the expression of RACGAP1. We also identified that RACGAP1 knockdown eliminated the stimulatory effects of MAGI2-AS3 silencing on the malignant phenotypes of HCC cells. Additionally, the expression of MAGI2-AS3 reduced tumor weight and size in HCC transplanted nude mice. Taken together, the key observations of the current study demonstrate the potential of MAGI2-AS3 as a tumor suppressor and a promising target for HCC treatment.

SUBMITTER: Pu J

PROVIDER: S-EPMC6807294 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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lncRNA MAGI2-AS3 Prevents the Development of HCC via Recruiting KDM1A and Promoting H3K4me2 Demethylation of the RACGAP1 Promoter.

Pu Jian J Wang Jianchu J Wei Huamei H Lu Tao T Wu Xianjian X Wu Yi Y Shao Zesheng Z Luo Chunying C Lu Yan Y

Molecular therapy. Nucleic acids 20190828

Accumulating studies have implicated the role of long non-coding RNAs (lncRNAs) in the pathogenesis of hepatocellular carcinoma (HCC) through the regulating transcription and mRNA stability. A recent report has linked Rac GTPase-activating protein 1 (RACGAP1) to the early recurrence of HCC. The current study aimed to ascertain whether MAGI2 antisense RNA 3 (MAGI2-AS3) influences the development of HCC by regulating RACGAP1. MAGI2-AS3 expression was initially quantified in both the HCC tissues an ...[more]

PMID: 31629962

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Project description:BackgroundLung cancer is a malignant tumor that seriously threatens the health of human beings. Long non-coding RNAs (lncRNAs) are thought to play important roles in the pathophysiology of lung cancer. In this study, we identified a new lncRNA, MAGI2-AS3 in non-small cell lung cancer (NSCLC) tissues by conducting an integrated bioinformatics analysis. Mechanistic studies were also performed to explore the biological functions of MAGI2-AS3 in NSCLC progression.MethodsA bioinformatics analysis was conducted to determine the prognostic role of MAGI2-AS3. CCK-8, EdU assay, colony formation and Transwell were performed to determine the effects of MAGI2-AS3 on the progression of NSCLC cells. A nude mice model was used to evaluate the effects of MAGI2-AS2 on the in vivo tumor growth of NSCLC. Luciferase reporter and RNA pull-down assays were used to evaluate interactions between MAGI2-AS3 and its downstream targets.ResultsMAGI2-AS3 was found to be downregulated in NSCLC tissues. The gain-of-function in vitro studies showed that the overexpression of MAGI2-AS3 suppressed NSCLC cell proliferation and invasion. Conversely, the knockdown of MAGI2-AS3 had the opposite effects. The bioinformatics analysis and luciferase report assay revealed that MAGI2-AS3 functioned as competing endogenous RNA to suppress microRNA (miR)-629-5p expression, while miR-629-5p suppressed thioredoxin-interacting protein (TXNIP) expression by targeting its 3' untranslated region. The rescue experiment results showed that MAGI2-AS3 knockdown enhanced NSCLC cell progression (increasing cell proliferation and invasion, but reducing cell apoptosis), which was counteracted by miR-629-5p inhibition or TXNIP overexpression.ConclusionsThe study revealed that MAGI2-AS3 was downregulated in NSCLC tissues and cells, and MAGI2-AS3 suppressed NSCLC cell progression. Further, the mechanistic results showed that MAGI2-AS3 exerted a tumor-suppressive effect in NSCLC by targeting the miR-629-5p/TXNIP axis.

Dataset Information

LncRNA MAGI2-AS3 Prevents the Development of HCC via Recruiting KDM1A and Promoting H3K4me2 Demethylation of the RACGAP1 Promoter.

Publications

lncRNA MAGI2-AS3 Prevents the Development of HCC via Recruiting KDM1A and Promoting H3K4me2 Demethylation of the RACGAP1 Promoter.

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