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MicroRNA-129-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting DNMT3A.

ABSTRACT: BACKGROUND:Glioma is the most common malignant tumor in the adult human brain and has one of the lowest patient survival rates. MicroRNAs (miRNAs) play important roles in the development of cancers, including glioma, and potentially have valuable therapeutic applications in glioma; however, their specific functions and mechanisms of action have yet to be fully defined. Here, we report that miR-129-5p directly targets DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and functions as a tumor-suppressor in glioma. METHOD:We analyzed the expression profiles of miR-129-5p and DNMT3A in glioma-related databases. Quantitative reverse transcription-PCR was applied to detect the level of miR-129-5p in glioma specimens and cell lines. Western blotting was applied to detect the level of DNMT3A. We examined the effect of miR-129-5p on the cell cycle and proliferation of glioma cells using CCK-8 and EDU assays and flow cytometry. TargetScan software predicted DNMT3A to be a target of miR-129-5p, which we confirmed by means of luciferase reporter assays and rescue experiments. RESULT:miR-129-5p was expressed at low levels in glioma and negatively correlated with glioma grade. Over-expression of miR-129-5p in U87and LN229 cells inhibited proliferation and blocked the cell cycle in G1 Phase. DNMT3A is a direct target of miR-129-5p, and miR-129-5p affects glioma cell proliferation by targeting DNMT3A. CONCLUSION:Taken together, our results demonstrate that miR-129-5p plays a significant role in glioma suppression through inhibition of DNMT3A, which may provide a novel therapeutic strategy for treatment of glioma and other DNMT3A-driven cancers.

SUBMITTER: Gu X

PROVIDER: S-EPMC6176228 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MicroRNA-129-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting DNMT3A.

Gu Xuhui X Gong Hui H Shen Lili L Gu Qingfeng Q

American journal of translational research 20180915 9

<h4>Background</h4>Glioma is the most common malignant tumor in the adult human brain and has one of the lowest patient survival rates. MicroRNAs (miRNAs) play important roles in the development of cancers, including glioma, and potentially have valuable therapeutic applications in glioma; however, their specific functions and mechanisms of action have yet to be fully defined. Here, we report that miR-129-5p directly targets DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and functions as a tumor ...[more]

PMID: 30323870

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Project description:Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. Acquiring a better understanding of the pathogenic mechanisms is essential to the design of effective therapeutic strategies. Previous studies have found that miR-520d-5p was negatively correlated with glioma grade, but its role and mechanism in glioma progression remain largely unknown. In the present study, we reported that miR-520d-5p directly targeted the Pituitary Tumor Transforming Gene 1 (PTTG1) and functioned as a tumor-suppressor in glioma. The expression of miR-520d-5p in glioma cells and specimens were detected by Quantitative reverse transcription-PCR and Fluorescence in situ hybridization (FISH). The effects of miR-520d-5p on glioma progression was examined by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. Using bioinformatics and luciferase reporter assays, we identified PTTG1 as a novel and direct target of miR-520d-3p. A xenograft model was used to study the effect of miR-520d-5p on tumor growth and angiogenesis. We found that miR-520d-5p expression was significantly decreased in glioma cell lines and tissues. Overexpression of miR-520d-5p showed a significant inhibitory effect on cell proliferation and accompanied cell cycle G0/G1 arrest in U87-MG and LN229 glioma cells. PTTG1 was a novel and direct target of miR-520d-5p, and the protein expression of PTTG1 was markedly reduced after overexpression of miR-520d-5p in U87-MG and LN229 cells. Overexpression of PTTG1 reversed the inhibitory effect of miR-520d-5p on glioma cell proliferation. In vivo studies confirmed that miR-520d-5p overexpression retarded the growth of U87 xenograft tumors, which was accompanied by reduced expression of PTTG1. In conclusion, these results provide compelling evidence that miR-520d-5p functions as an anti-onco-miRNA, which is important in inhibiting cell proliferation in GBM, and its anti-oncogenic effects are mediated chiefly through direct suppression of PTTG1 expression. Therefore, we suggest that miR-520d-5p is a potential candidate for the prevention of glioblastoma.

Dataset Information

MicroRNA-129-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting DNMT3A.

Publications

MicroRNA-129-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting DNMT3A.

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