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Epigenetic regulation of miR-129-2 and its effects on the proliferation and invasion in lung cancer cells.

ABSTRACT: MicroRNAs (miRNAs) play a pivotal role in carcinogenesis. Dysregulation of miRNAs, both oncogenic miRNAs and tumour-suppressive miRNAs, is closely associated with cancer development and progression. The levels of miRNAs could be changed epigenetically by DNA methylation in the 5' untranslated region (UTR) of pre-mature miRNAs. To investigate whether DNA methylation alters the expression of miR-129 in lung cancer, we did DNA methylation assays and found that 5' UTR region of miR-129-2 gene was absolutely methylated in both A549 and SPCA-1 lung cancer cells, but totally un-methylated in 95-D cells. The expression of miR-129 was restored by 5-Aza-2'-deoxycytidine (DAC), a de-methylation agent, in both A549 and SPCA-1 cells, resulting in attenuated cell migration and invasion ability, and decreased protein level of NF-κB, which indicates the involvement of NF-κB pathway. To further illustrate the roles of miR-129 in lung tumourigenesis, we overexpressed miR-129 in lung cancer cells by transfection of miR-129 mimics, and found arrested cell proliferation at G2/M phase of cell cycle and inhibited cell invasion. These findings strongly suggest that miR-129 is a tumour suppressive miRNA, playing important roles in the development and progression of human lung cancer.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC4568922 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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Epigenetic regulation of miR-129-2 and its effects on the proliferation and invasion in lung cancer cells.

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