Tumor invasion and metastasis regulated by microRNA-184 and microRNA-574-5p in small-cell lung cancer

Abstract

// Rui Zhou 1, * , Xiaoshu Zhou 1, * , Zhongyuan Yin 1 , Jing Guo 2 , Ting Hu 1 , Shun Jiang 3 , Li Liu 1 , Xiaorong Dong 1 , Sheng Zhang 1 , Gang Wu 1 1 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Department of Oncology of The Affiliated Hospital of Qingdao University, Qingdao, China 3 Department of Oncology, Second Xiangya Hospital of Central South University, Changsha, China * These authors have contributed equally to this work Correspondence to: Gang Wu, e-mail: xhzlwg@163.com Keywords: miR-184, miR-574-5p, metastasis, prognosis, SCLC Received: April 18, 2015      Accepted: November 06, 2015      Published: November 16, 2015 ABSTRACT Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that has an extremely poor clinical prognosis. Metastasis is the key event in SCLC progression, but its mechanism has not been fully elucidated. MicroRNAs (miRNAs) have been proven to participate in cancer processes, but their function in SCLC has not been thoroughly studied either. Here, we performed microarray and quantitative real-time PCR (qRT-PCR) analysesto identify the miRNAsassociated with metastasis and prognosis in SCLC as well as the correlation between serum and tissue. We also explored these miRNAs’ promising molecular mechanisms by 3′UTR reporter assay and immunoblotting. We showed thatmiR-184 significantly attenuated the metastasis of SCLC, whereas miR-574–5p enhanced it. Both miRNAs were found to participate in β-catenin signaling by suppressing protein tyrosine phosphatase receptor type U (PTPRU)orendothelial PAS domain protein 1 (EPAS1). Furthermore, miR-574–5p was verified as an independent prognostic risk factor for SCLC. Taken together, our findings providea comprehensive analysis of the miRNA expression pattern in SCLC and indicate that miRNAs may serve as potential therapeutic and prognostic predictors in SCLC.