miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells

Molecular Cancer

Research

Yiping Wang¹  Jipeng Li¹  Wanjun Yu²  Yulan Song³  Zhongming Fu⁴ 

[1] Department of Clinical Laboratory, Yinzhou People’s Hospital, 315040, Ningbo, China;Department of Clinical Laboratory, Yinzhou People’s Hospital, 315040, Ningbo, China;Department of Respiratory and Critical Care Medicine, Yinzhou People’s Hospital, 251 East Baizhang Road, 315040, Ningbo, China;Department of Nephrology, Yinzhou People’s Hospital, 315040, Ningbo, China;Department of Respiratory and Critical Care Medicine, Yinzhou People’s Hospital, 251 East Baizhang Road, 315040, Ningbo, China;

关键词: miR-27a;    RKIP;    Lung adenocarcinoma;    Cisplatin;    Chemoresistance;   

DOI  :  10.1186/1476-4598-13-193

 received in 2014-05-15, accepted in 2014-08-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood.MethodsWe detected miR-27a expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-27a on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-27a level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens.ResultsmiR-27a was significantly up-regulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-27a regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified Raf Kinase Inhibitory Protein (RKIP) as a direct and functional target of miR-27a. Small interfering RNA-mediated RKIP knockdown revealed similar effects as that of ectopic miR-27a expression, while overexpression of RKIP attenuated the function of miR-27a in lung adenocarcinoma cells. Increased miR-27a expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of RKIP, decreased sensitivity to cisplatin, and poor prognosis.ConclusionOur results suggest that up-regulation of miR-27a could suppress RKIP expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin.

【 授权许可】

CC BY   
© Li et al.; licensee BioMed Central Ltd. 2014