Micro-RNA-155 is induced by K-Ras oncogenic signal and promotes ROS stress in pancreatic cancer

// Peng Wang 1,2,* , Chao-feng Zhu 1,* , Ming-zhe Ma 1,* , Gang Chen 3,* , Ming Song 1 , Zhao-lei Zeng 1 , Wen-hua Lu 1 , Jing Yang 1 , Shijun Wen 1 , Paul J. Chiao 4 , Yumin Hu 1 and Peng Huang 1,3 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 2 Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Guangzhou, China 3 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors contributed equally to this work Correspondence to: Yumin Hu, email: // Peng Huang, email: // Keywords : K-Ras, miR-155, reactive oxygen species, pancreatic cancer Received : November 05, 2014 Accepted : May 02, 2015 Published : May 12, 2015 Abstract The oncogenic K-Ras can transform various mammalian cells and plays a critical role in development of pancreatic cancer. MicroRNAs (miRNA) have been shown to contribute to tumorigenic progression. However, the nature of miRNAs involved in K-Ras transformation remains to be investigated. Here, by using microarray we identified miR-155 as the most upregulated miRNA after both acute and prolonged activation of K-Ras in a doxycyline-inducible system. Pharmacological inhibition of MAPK and NF-κB pathway blocked the induction of miR-155 in response to K-Ras activation. Overexpression of miR-155 caused inhibition of Foxo3a, leading to decrease of major antioxidants including SOD2 and catalase, and enhanced pancreatic cell proliferation induced by ROS generation. Importantly, correlations of K-Ras, miR-155 and Foxo3a were also validated in human pancreatic cancer tissues. Therefore, we propose that miR-155 plays an important role in oncogenic K-Ras transformation mediated by cellular redox regulation.