Downregulation of miR-17~92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN.docVIP

Int. J. Mol. Sci. 2013, 14, 3802-3816; doi:10.3390/ijmOPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Article Downregulation of miR-17~92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN Ting Shuang , Chunxue Shi 1,2,?, Shuang Chang 1,?, Min Wang * and Cui Hong Bai 1 1 1, 1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China; E-Mails: shuangting87@163.com (T.S.); c.shuang-0519@163.com (S.C.); myearth126@126.com (C.H.B.) 2 Shenyang Maternity and infant Hospital, 90 Qingnian Road, Shenhe District, Shenyang 110014, China; E-Mail: shichunxue_502@163.com ? These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: wm21st@; Tel.: +86 Fax: +86-024-8395-5092. Received: 24 December 2012; in revised form: 23 January 2013 / Accepted: 4 February 2013 / Published: 8 February 2013 Abstract: To better understand the molecular mechanisms of paclitaxel resistance in ovarian carcinoma, we evaluated the expression of miRNAs using miRNA microarray between human ovarian carcinoma SKOV3 cells and paclitaxel resistant SKOV3-TR30 cells. Results showed that 69 miRNAs were upregulated while 102 miRNAs were downregulated in SKOV3-TR30 cells. Using real-time PCR, we further clarified that miR-17~92 was overexpressed in SKOV3-TR30 cells compared with that in SKOV3 cells. We then established stable virally transduced SKOV3-TR30-m-PTIP-Sponge all SKOV3-TR30 cells and its vector-only control SKOV3-TR30-m-PTIP-GFP cells. Real time-PCR revealed that SKOV3-TR30-m-PTIP-Sponge all cells expressed approximately 6.18-fold lower levels of miR-17~92 compared with the control group. Decreased expression of miR-17~92 resulted in cell cycle arrest in the G2/M pha