MicroRNA-155 promotes apoptosis in SKOV3, A2780, and primary cultured ovarian cancer cells.

Wei Chen, Liuxuan Huang, Chenjun Hao, Wenshu Zeng, Xu Luo, Xiaodi Li, Longshu Zhou, Songshan Jiang, Zheng Chen, Yuanli He,

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, January 18, 2016

MicroRNAs (miRNAs) are a large group of small non-coding RNAs that can negatively regulate gene expression at the post-transcriptional level. The deregulation of miRNAs has been associated with tumorigenesis, drug resistance, and prognosis in cancers. Deregulated miR-155 has been reported in numerous cancers; however, its function remains unclear. 4’,6-Diamidino-2-phenylindole (DAPI) staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) techniques were used to determine the effects of a miR-155 mimic or inhibitor on the apoptotic ratio of ovarian cancer cells induced by cisplatin. Bioinformatic predictions, the dual-luciferase reporter assay, and western blot analysis were used to detect how miR-155 regulates X-linked inhibitor of apoptosis protein (XIAP). We demonstrated that a miR-155 mimic could decrease the IC50 value of cisplatin in SKOV3 ovarian cancer cells. Subsequently, gain- and loss-of-function analyses with a miR-155 mimic and inhibitor showed that miR-155 sensitizes ovarian cancer cells to cisplatin. Furthermore, the results from the luciferase assays and western blot analysis identified XIAP as the direct target of miR-155. In addition, introducing XIAP cDNA without a three prime untranslated region (3’-UTR) rescued the miR-155 promotion of apoptosis. These results indicate that miR-155 mediates cisplatin-induced apoptosis by targeting XIAP in ovarian cancer cells and that miR-155 could be a potential therapeutic target to increase the efficiency of ovarian cancer interventions.

Pubmed Link: 26779627