MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma

// Ling Chen 1, 2 , Guangming Kong 3 , Chuantao Zhang 1 , Hongyan Dong 4 , Cuicui Yang 4 , Guanhua Song 5 , Chengye Guo 2 , Lin Wang 6 , Hongsheng Yu 1 1 Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, China 2 Department of Oncology, Qingdao Municipal Hospital, Qingdao, China 3 Emergency Department, Qingdao Municipal Hospital, Qingdao, China 4 Department of Pathology, Linyi People’s Hospital, Linyi, China 5 Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China 6 Research Center for Medicinal Biotechnology, Key Laboratory for Rare and Uncommon Diseases of Shandong Province, Shandong Academy of Medical Sciences, Jinan, China Correspondence to: Hongsheng Yu, e-mail: hshyu2015@163.com Lin Wang, e-mail: kecheng1216@163.com Keywords: lung adenocarcinoma, miR-432, E2F3, AXL Received: August 05, 2015      Accepted: January 31, 2016      Published: March 03, 2016 ABSTRACT Abnormal proliferation and drug resistance are the hallmarks of lung adenocarcinoma (LAD). Dispite the advances in diagnosis and therapy, the 5-year survival remains low. Increasing studies regarding its pathological mechanism have been focused on microRNA (miRNA) due to its nodal regulatory properties. This study aims to characterize the expression of miR-432 in LAD and investigate its effects on the proliferation and sensitivity of lung cancer cells to cisplatin. Here, we report that downregulation of miR-432 in LAD tissues was correlated with a higher clinical stage ( p = 0.03) and poor prognosis ( p = 0.036). Additionally, miR-432 expression was negative correlated with high Ki67 labeling index ( p = 0.016) in our cohorts. Functionally, over-expression of miR-432 inhibits cell proliferation through arresting cell cycle and sensitizes tumor cells to cisplatin. Mechanistically, miR-432 functions by directly targeting E2F3 and AXL, and they, in turn, mediate the regulation of miR-432 towards cell proliferation and cisplatin sensitivity. Importantly, miR-432 levels are negatively correlated with the levels of E2F3 and AXL in human LAD tissues. These results demonstrated that miR-432 functions as a tumor-suppressive miRNA and may represent a prognostic parameter and therapeutic target for LAD.