MiR-650 represses high-risk non-metastatic colorectal cancer progression via inhibition of AKT2/GSK3β/E-cadherin pathway

// Chunxian Zhou 1, 2, * , Fengyun Cui 1, * , Jiali Li 1, * , Diyi Wang 1 , Yingze Wei 1 , Ying Wu 1, # , Jiping Wang 3 , Hongguang Zhu 1 and Shuyang Wang 1 1 Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China 2 Department of Pathology, Shanghai University of Traditional Chinese Medicine, Shanghai, China 3 Division of Surgical Oncology, Brigham and Women Medicine, Harvard Medical School, Boston, Massachusetts, USA # Dedication: We would like to dedicate this paper to Professor Ying Wu, who unfortunately passed away in 2015. Professor Ying Wu played an essential role in this study and she is greatly missed * These authors contributed equally to this work Correspondence to: Shuyang Wang, email: shuyangwang@fudan.edu.cn Hongguang Zhu, email: hongguang_701@shmu.edu.cn Keywords: non-metastatic colorectal cancer, prognosis biomarker, microRNA, AKT pathway Received: October 12, 2016      Accepted: April 24, 2017      Published: May 10, 2017 ABSTRACT Although 5-year survival rate of non-metastatic colorectal cancer (CRC) is high, about 10% of patients in stage I and II still develop into metastatic CRC and eventually die after resection. Currently, there is no effective biomarker for predicting the prognosis of non-metastatic CRC in clinical practice. In this study, we identified miR-650 as a biomarker for prognosis prediction. We observed that the expression of miR-650 in tumor tissues had a positive association with overall survival. MiR-650 inhibited cell growth and invasion in vitro and in vivo . Furthermore, miR-650 targeted AKT2 and repressed the activation of the AKT pathway (AKT2/GSK3β/E-cadherin). Thus it induced the translocation of E-cadherin and β-catenin in cancer cells. Our results highlight the potential of miR-650 as a prognostic prediction biomarker and therapeutic target in non-metastatic CRC via inhibition of the AKT2/GSK3β/E-cadherin pathway.