Inhibition of miR-574-5p suppresses cell growth and metastasis and enhances chemosensitivity by targeting RNA binding protein QKI in cervical cancer cells.

Abstract

Cervical cancer is the fourth most common female malignancy worldwide and microRNA (miR)-574-5p is a candidate oncogene in multiple cancers. The present study aimed to investigate the role and mechanism of miR-574-5p in cervical cancer. miR-574-5p inhibitors or mimics were transfected into cervical cancer cells to study the function of miR-574-5p. The effects of miR-574-5p on cell growth, invasion, and chemosensitivity were evaluated using CCK8, flow cytometry, transwell, immunofluorescence, and Western blotting analysis. Further depletion or forced expression of QKI was performed to explore the regulatory mechanism of miR-574-5p in cervical cancer. Up-regulation of miR-547-5p and down-regulation of QKI were observed in 30 cervical cancer tissues versus 30 adjacent normal tissues. Silencing of miR-574-5p increased apoptosis, inhibited proliferation, cell cycle progression, and cell invasiveness, as well as enhanced chemosensitivity towards cisplatin and doxorubicin in cervical cancer cells. Overexpression of miR-574-5p exerted promoting effect on cancer progression and metastasis. Knockdown of miR-574-5p induced an up-regulation of E-cadherin and down-regulation of cyclinD1, N-cadherin, matrix metallopeptidase 9 (MMP-9), and β-catenin in cervical cancer cells Moreover, QKI was verified as a target of miR-574-5p and involved in regulation of miR-574-5p-induced cervical cancer cell progression and metastasis. miR-574-5p functions to be oncogenic in cervical cancer, and its inhibition suppresses cervical cancer progression and metastasis as well as enhances chemosensitivity by targeting QKI. Therefore, miR-574-5p is suggested as a potential therapeutic target for cervical cancer treatment.