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Inhibition of cell proliferation and migration by miR-509-3p that targets CDK2, Rac1, and PIK3C2A.

ABSTRACT: CDK2 is a key regulator of cell cycle progression. In this study, we screened for miRNAs targeting CDK2 using a luciferase-3'-untranslated region reporter assay. Among 11 hit miRNAs, miR-509-3p reduced CDK2 protein levels and significantly inhibited cancer cell growth. Microarray, Western blotting, and luciferase reporter analyses revealed additional targets of miR-509-3p, including Rac1 and PIK3C2A. Overexpression of miR-509-3p induced G1 cell-cycle arrest and inhibited colony formation and migration. RNAi experiments indicated that the growth-inhibitory effects of miR-509-3p may occur through down-regulation of CDK2, Rac1, and PIK3C2A. Targeting of multiple growth regulatory genes by miR-509-3p may contribute to effective anti-cancer therapy.

SUBMITTER: Yoon S

PROVIDER: S-EPMC4012080 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Inhibition of cell proliferation and migration by miR-509-3p that targets CDK2, Rac1, and PIK3C2A.

Yoon Sena S Han Eunji E Choi Young-Chul YC Kee Honghwan H Jeong Yongsu Y Yoon Jaeseung J Baek Kwanghee K

Molecules and cells 20140421 4

CDK2 is a key regulator of cell cycle progression. In this study, we screened for miRNAs targeting CDK2 using a luciferase-3'-untranslated region reporter assay. Among 11 hit miRNAs, miR-509-3p reduced CDK2 protein levels and significantly inhibited cancer cell growth. Microarray, Western blotting, and luciferase reporter analyses revealed additional targets of miR-509-3p, including Rac1 and PIK3C2A. Overexpression of miR-509-3p induced G1 cell-cycle arrest and inhibited colony formation and mig ...[more]

PMID: 24802056

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Project description:Centromere coiled-coil protein 110 (CCP110) plays a role in the development of several types of cancer; however, its regulatory mechanism and role in endometrial cancer is unclear. The present study revealed that CCP110 is regulated by a signaling pathway involving microRNA (miR/miRNA)-129-2-3p and the long non-coding RNA (lncRNA) X-inactive-specific transcript (XIST), and plays a role in controlling the proliferation, migration and invasion of endometrial cancer cells. CCP110 was upregulated in human endometrial cancer tissues, as revealed by immunohistochemistry, and high expression of the protein was related to reduced overall survival of the patients. Genetic knockdown of CCP110 by small interfering RNA promoted apoptosis and suppressed the proliferation, migration, invasion and colony formation of endometrial cancer cells significantly in the endometrial cancer Ishikawa and HEC-1B cell lines, as assessed by flow cytometry, and Cell Counting Kit-8, Transwell and colony formation assays. A bioinformatics analysis and luciferase reporter assay revealed that CCP110 is a target of miR-129-2-3p. Overexpression of miR-129-2-3p mimic fragments inhibited the proliferation, migration and invasion of endometrial cancer cells significantly, while co-overexpression of CCP110 counteracted these inhibitory effects. The expression level of the lncRNA XIST was upregulated significantly in endometrial cancer tissues, as assessed by reverse transcription-quantitative PCR assay, while that of miR-129-2-3p was downregulated significantly. A bioinformatics analysis and luciferase reporter assay showed that XIST could inhibit miR-129-2-3p via a miRNA sponge effect. Furthermore, co-overexpression of XIST antagonized the inhibitory effect of the miR-129-2-3p mimic on the luciferase reporter gene signal and protein expression of CCP110. Co-overexpression of XIST also abolished the inhibitory effect of the miR-129-2-3p mimic on the proliferation, migration and invasion of endometrial cancer cells. Overall, these data identified a novel regulatory mechanism of CCP110 involving XIST and miR-129-2-3p, which affected the development of endometrial carcinoma. CCP110, XIST and miR-129-2-3p could represent novel targets for the clinical treatment of endometrial cancer.

Dataset Information

Inhibition of cell proliferation and migration by miR-509-3p that targets CDK2, Rac1, and PIK3C2A.

Publications

Inhibition of cell proliferation and migration by miR-509-3p that targets CDK2, Rac1, and PIK3C2A.

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