MiR-498 regulated FOXO3 expression and inhibited the proliferation of human ovarian cancer cells
 

Biomedicine & Pharmacotherapy doi:10.1016/j.biopha.2015.04.005 

Ruonan Liu^a,Fenghu^a Liua,Lei Li^a,Miaomiao Sun^b,Kuisheng Chen^c

 

^a Department of Gynecology, Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, People's Republic of China

^b Pathological Department, Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, People's Republic of China

^c Department of Pathology and Pathological Physiology, Basic Medical College of Zhengzhou University, Zhengzhou 450052, People's Republic of China

 

Abstract

Ovarian cancer is one of the most common human malignancies and the fifth leading cause of cancer deaths in women. Thus, improved approaches for detection of ovarian cancer are urgently needed. Recently, microRNAs (miRNAs) have been suggested to be closely associated with ovarian cancer tumorigenesis. In the current study, our study showed that expression of miR-498 was markedly downregulated in ovarian cancer cells and ovarian cancer tissues compared with human ovary surface epithelial cells (HOSE) and the matched tumor adjacent normal tissues (ANT). Ectopic expression of miR-498 suppressed cell proliferation of ovarian cancer cells, while i miR-498-in showed the opposite effect. Furthermore, upregulation of miR-498 in ovarian cancer cells resulted in blocking of their entry into the S transitional phase, which was caused by downregulation of the CDK regulator cyclin D1 and upregulation of cyclin-dependent kinase inhibitor p27. Additionally, we identified FOXO3 as a direct target of miR-498. Moreover, we demonstrated that miR-498 upregulated FOXO3 expression by directly targeting the FOXO3 3′-untranslated region. Thus, our findings suggested that miR-498 acted as a new tumor suppressor by targeting the FOXO3 gene and inhibiting cell proliferation of ovarian cancer.