title: Downregulation of miR-17&#126;92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN.
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 phase and growth inhibition. After the transduction, the BIM protein level was increased in SKOV3-TR30 cells and luciferase reporter assays revealed that miR-17~92 binds directly to the 3'-UTR of BIM. Results of luciferase reporter assays accompanied with Western Blot showed that although miR-17~92 binds directly to the 3'-UTR of PTEN, the PTEN protein expression level was upregulated slightly while the result is of no statistical significance. Our results showed that miR-17~92 could be a causal factor of the downregulation of BIM in  SKOV3-TR30 cells and thus induce the paclitaxel resistance in SKOV3-TR30 cells.
authors: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China. wm21st@hotmail.com.
authors: Ting
authors: T
authors: Shuang
authors: Chunxue
authors: C
authors: Shi
authors: Shuang
authors: S
authors: Chang
authors: Min
authors: M
authors: Wang
authors: Cui Hong
authors: CH
authors: Bai
references: Cancer Cell. 2002 Sep;2(3):183-92
references: 12242151
references: Mol Cell. 2007 Jul 6;27(1):91-105
references: 17612493
references: Science. 2007 Feb 9;315(5813):856-9
references: 17289999
references: Cancer Lett. 2008 Nov 28;271(2):260-71
references: 18657898
references: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references: 20610543
references: Nat Rev Genet. 2008 Feb;9(2):102-14
references: 18197166
references: Cell. 2003 Dec 26;115(7):787-98
references: 14697198
references: Nat Med. 2005 Jul;11(7):712-4
references: 16015356
references: Cancer Genet. 2012 May;205(5):212-9
references: 22682620
references: Mol Cell. 2005 Feb 18;17(4):525-35
references: 15721256
references: Gene Ther. 2003 Sep;10(19):1636-42
references: 12923562
references: Nat Rev Cancer. 2006 Nov;6(11):857-66
references: 17060945
references: Int J Biochem Cell Biol. 2010 Aug;42(8):1273-81
references: 20026422
references: J Biol Chem. 2011 Jun 24;286(25):22384-92
references: 21561860
references: Nat Immunol. 2008 Apr;9(4):405-14
references: 18327259
references: PLoS One. 2012;7(8):e44095
references: 22952885
references: Nature. 2005 Jun 9;435(7043):828-33
references: 15944707
references: Leuk Res. 2012 Dec;36(12):1505-9
references: 22959509
references: Nat Rev Cancer. 2006 Apr;6(4):259-69
references: 16557279
references: PLoS One. 2011 Feb 24;6(2):e16408
references: 21383985
references: Biochim Biophys Acta. 2010 Apr;1805(2):209-17
references: 19931352
references: Cancer Res. 2004 May 1;64(9):3087-95
references: 15126345