Tanshinones suppress AURKA through up-regulation of miR-32 expression in non-small cell lung cancer

Abstract

// Zhong-Liang Ma 1, * , Bing-Jie Zhang 1, * , De-Tao Wang 1 , Xue Li 1 , Jia-Li Wei 1 , Bo-Tao Zhao 1 , Yan Jin 2 , Yan-Li Li 1 , You-Xin Jin 1, 3 1 School of Life Sciences, Shanghai University, Shanghai 200444, China 2 Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China 3 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China * These authors have contributed equally to this work Correspondence to: You-Xin Jin, e-mail: jinyouxin@shu.edu.cn Yan-Li Li, e-mail: liyanli@shu.edu.cn Yan Jin, e-mail: yan.jin@siat.ac.cn Keywords: tanshinone, AURKA, miRNA, non-small cell lung cancer Received: January 26, 2015      Accepted: May 04, 2015      Published: May 14, 2015 ABSTRACT Tanshinone is the liposoluble constituent of Salia miltiorrhiza , a root used in traditional herbal medicine which is known to possess certain health benefits. Although it is known that tanshinones, including tanshinone I (T1), tanshinone IIA (T2A), and cryptotanshinone (CT), can inhibit the growth of lung cancer cells in vitro , the mechanism under which they act is still unclear. AURKA, an oncogene, encodes a serine-threonine kinase which regulates mitotic processes in mammalian cells. Here, we reported that tanshinones mediate AURKA suppression partly through up-regulating the expression of miR-32. We found that tanshinones could inhibit cell proliferation, promote apoptosis, and impede cell-cycle progression, thus performing an antineoplastic function in non-small cell lung cancer (NSCLC). Additionally, we demonstrated that tanshinones attained these effects in part by down-regulating AURKA, corroborating previous reports. Our results showed that in NSCLC, similar effects were obtained with knock-down of the AURKA gene by siRNA. We also verified that AURKA was the direct target of miR-32. Collectively, our results demonstrated that tanshinones could inhibit NSCLC by suppressing AURKA via up-regulating the expressions of miR-32 and other related miRNAs.