Downregulation of miR‐29 contributes to cisplatin resistance of ovarian cancer cells. Issue 3 (28th August 2013)

• Record Type: Journal Article
• Authors: Yu, Pei‐Ning; Yan, Ming‐De; Lai, Hung‐Cheng; Huang, Rui‐Lan; Chou, Yu‐Ching; Lin, Wen‐Chi; Yeh, Li‐Tzu; Lin, Ya‐Wen
• Is Part Of: International journal of cancer. Volume 134:Issue 3(2014:Feb. 01)
• Page Start: 542
• Page End: 551
• Publication Date: 2013-08-28
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28399
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Drug resistance is an obstacle to the treatment of ovarian cancer. Using a unique cell model, we have proven previously that a subpopulation of ovarian cancer cells is more resistant to cisplatin than are the original cells. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells. In our study, we explored whether miRNAs are involved in cisplatin resistance of ovarian cancer cells. Cisplatin‐resistant cells expressed a lower level of <italic>miR‐29a/b/c</italic>. Manipulation of microRNA‐29 (<italic>miR‐29</italic>) expression modulated cisplatin sensitivity of CP70, HeyC2, SKOV3 and A2780 ovarian cancer cells. Knockdown of <italic>miR‐29a/b/c</italic> increased the ability of cells to escape cisplatin‐induced cell death partly through upregulation of collagen type I alpha 1 (COL1A1) and increased the activation of extracellular signal‐regulated kinase 1/2 and inactivation of glycogen synthase kinase 3 beta. When combined with cisplatin treatment, knockdown of <italic>miR‐29</italic> decreased the amount of the active form of caspase‐9 and caspase‐3. Ectopic expression of <italic>miR‐29</italic> alone or in combination with cisplatin treatment efficaciously reduced the tumorigenicity of CP70 cells <italic>in vivo</italic>. Our data show that downregulation of <italic>miR‐29</italic> increases cisplatin resistance in ovarian cancer cells. Taken together, these data suggest that overexpression of <italic>miR‐29</italic> is a potential sensitizer to cisplatin treatment that may have therapeutic implications.</p> </abstract>