miR-22-Notch Signaling Pathway Is Involved in the Regulation of the Apoptosis and Autophagy in Human Ovarian Cancer Cells

抄録

microRNA-22 (miR-22) is a brain-enriched regulatory gene which has been reported to be involved in the development of cancers. The Notch signaling pathway exerts important functions in cell growth. This study is designed to investigate the mechanisms of miR-22-Notch signaling pathway in apoptosis and autophagy of human ovarian cancer cells. After over-expressing miR-22 in human ovarian cancer cell lines OVCAR-3 and SKOV3, cell viability is determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method, cell apoptosis is observed by Flow cytometry (FCM), mRNA expression of miR-22 is measured by RNA preparation and RT-PCR, protein expression of Notch1, Hes1, Beclin1 and LC3B-II is analyzed by Western blot. It is suggested that miR-22 expression is heavily decreased in human ovarian cancer cell lines OVCAR-3 and SKOV3. Over-expression of miR-22 potently suppresses cell viability and authophagy while promotes the percentage of apoptotic cancer cells. In addition, the decreased expression level of Notch1 and its targeted gene is detected in miR-22-over-expressed cells. Moreover, followed by the block of the Notch signaling pathway using Notch1 small interference RNA (siRNA), the effects of miR-22 on the apoptosis and autophagy of human ovarian cancer cell lines OVCAR-3 and SKOV3 are obviously blocked. Together, miR-22 inhibits apoptosis and promotes autophagy of human ovarian cancer cells through the suppression of the Notch signaling pathway, indicating a potential use of miR-22 in the ovarian cancer treatment.