MiR-494 inhibits cervical cancer cell proliferation through upregulation of SOCS6 expression.

Abstract

It is unclear how microRNA (miR)-494 inhibits the proliferation of cervical cancer cells by altering the expression of SOCS6. Therefore, the present study aimed to investigate the molecular mechanism underlying miR-494 regulation of suppressor of cytokine signaling 6 (SOCS6) in human cervical cancer samples and the human cervical cancer HeLa cell line. The expression of miR-494 was determined using reverse transcription-quantitative polymerase chain reaction. In addition, TargetScan was used to predict miR-494 target genes and the luciferase reporter assay was used to determine whether SOCS6 was a direct target of miR-494. The results of the present study demonstrated that compared with the cervical intraepithelial neoplasia and normal cervical tissues, the miR-494 expression level in cervical cancer samples was significantly decreased (P<0.01). In addition, compared with normal cervical tissue, miR-494 expression level was significantly decreased in cervical intraepithelial lesions (P<0.05). Furthermore, the expression of miR-494 was associated with patients with or without lymph node metastasis, clinical stage and depth of stromal invasion (P<0.01); however, miR-494 expression was not identified to be associated with age, tumor size and menopausal status (P>0.05). Transfection of a miR-494 mimic significantly increased the expression level of miR-494 in HeLa cells (P<0.01), and anti-miR-494 transfection decreased the expression of miR-494 (P<0.01). An MTT proliferation assay and Boyden chamber invasion ability assay revealed that miR-494 mimic transfection significantly inhibited the proliferation, and invasion ability of HeLa cells (P<0.01), whereas anti-miR-494 transfection significantly increased the proliferation and invasion ability (P<0.05). SOCS6 was predicted, using bioinformatics, to be the target gene of miR-494 and this was validated using a luciferase reporter assay. Western blot analysis revealed that transfection of miR-494 significantly increased the expression of SOCS6 in HeLa cells, and transfection of anti-miR-494 significantly decreased the expression of SOCS6. Therefore, the results of the present study demonstrated that miR-494 expression in cervical cancer was significantly decreased. Exhibiting a decreased expression level of miR-494 may result in enhanced proliferative and invasive abilities of HeLa cell, thus contributing to the occurrence, and development of cervical cancer.