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LncRNA MAGI2-AS3 inhibits bladder cancer progression by targeting the miR-31-5p/TNS1 axis.

ABSTRACT: In this study, we performed bioinformatics analysis to identify the competing endogenous RNAs (ceRNAs) that regulate bladder cancer (BCa) progression. RNA-sequencing data analysis identified 2451 differentially expressed mRNAs, 174 differentially expressed lncRNAs, and 186 microRNAs (miRNAs) in BCa tissues (n=414) compared to the normal urothelial tissues (n=19) from the TGCA database. CeRNA network analysis of the differentially expressed lncRNAs and mRNAs showed strong positive correlation between lncRNA MAGI2-AS3 and Tensin 1 (TNS1) mRNA in BCa tissues. Bioinformatics analysis also showed that both MAGI2-AS3 and TNS1 mRNA sequences contain miR-31-5p binding sites. Furthermore, we observed significantly lower MAGI2-AS3 and TNS1 mRNA expression and higher miR-31-5p expression in the BCa tissues and cell lines (T24 and J82) compared with their corresponding controls. Functional and biochemical experiments in BCa cell lines including luciferase reporter assays showed that MAGI2-AS3 upregulated TNS1 by sponging miR-31-5p. Transwell assays showed that the MAGI2-AS3/miR-31-5p/TNS1 axis regulated migration and invasion ability of BCa cell lines. Moreover, immunohistochemical staining of paired BCa and normal urothelial tissues showed that low expression of TNS1 correlated with advanced tumor (T) stages and lymph node metastasis in BCa. In conclusion, our study demonstrates that the MAGI2-AS3/miR-31-5p/TNS1 axis regulates BCa progression.

SUBMITTER: Tang C

PROVIDER: S-EPMC7803496 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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LncRNA MAGI2-AS3 inhibits bladder cancer progression by targeting the miR-31-5p/TNS1 axis.

Tang Congyi C Cai Yi Y Jiang Huichuan H Lv Zhengtong Z Yang Changzhao C Xu Haozhe H Li Zhi Z Li Yuan Y

Aging 20201120 24

In this study, we performed bioinformatics analysis to identify the competing endogenous RNAs (ceRNAs) that regulate bladder cancer (BCa) progression. RNA-sequencing data analysis identified 2451 differentially expressed mRNAs, 174 differentially expressed lncRNAs, and 186 microRNAs (miRNAs) in BCa tissues (n=414) compared to the normal urothelial tissues (n=19) from the TGCA database. CeRNA network analysis of the differentially expressed lncRNAs and mRNAs showed strong positive correlation bet ...[more]

PMID: 33231563

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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 inhibits bladder cancer progression by targeting the miR-31-5p/TNS1 axis.

Publications

LncRNA MAGI2-AS3 inhibits bladder cancer progression by targeting the miR-31-5p/TNS1 axis.

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