Τετάρτη 6 Φεβρουαρίου 2019

MiR-29a inhibits cell proliferation and migration by targeting the CDC42/PAK1 signaling pathway in cervical cancer

Cervical cancer is the second most common gynecological malignancy worldwide and the tumorigenesis mechanisms of cervical cancer are still unclear. This study aimed to reveal the role of miR-29a in cervical cancer. The expression level of miR-29a and CDC42 was measured using qRT-PCR. Cell proliferation, apoptosis, migration, and invasion were detected using colony formation, flow cytometry analysis, wound-healing assay, and Transwell assay, respectively. Luciferase reporter assay was used to determine the binding of miR-29a with CDC42. CDC42/p21-activated kinase 1 (PAK1) pathway-related proteins were measured by western blotting. MiR-29a was downregulated and CDC42 was upregulated in cervical cancer cells. Luciferase reporter assay showed that miR-29a negatively regulated the expression of CDC42 by directly targeting 3′-UTR of CDC42. Cell proliferation, migration, and invasion were markedly inhibited, whereas cell apoptosis was significantly increased in Hela and CaSki cells transfected with miR-29a mimics. These effects were partly recovered by CDC42 overexpression. Protein levels of PAK1, p-PAK1, p-LIMK, and p-cofilin were significantly downregulated by miR-29a mimics, which was reversed by CDC42 overexpression and was increased by the miR-29a inhibitor. MiR-29a inhibited cell proliferation, migration, and invasion, as well as promoted cell apoptosis through repressing the PAK1/LIMK signaling pathway by targeting CDC42 in cervical cancer. Correspondence to Rong Chen, Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Hunan Normal University, No. 89, Guhan Road, Furong District, Changsha, Hunan Province 410000, People's Republic of China Tel/fax: +86 139 7581 8202; e-mail: chenrong1778@163.com Received July 26, 2018 Accepted December 14, 2018 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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