Silencing protein kinase C ζ by microRNA-25-5p activates AMPK signaling and inhibits colorectal cancer cell proliferation

// Shihu Zhang 1, * , Yiyang Zhang 2, * , Qing Cheng 3, * , Zhaoqun Ma 1 , Guanwen Gong 1 , Zhengming Deng 1 , Kun Xu 1 , Gaoyuan Wang 1 , Yousong Wei 1 and Xiaoping Zou 2 1 Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China 2 Digestive Department, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, China 3 Department of Gynaecology and Obstetrics, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Yousong Wei, email: weiyousongnanjlw@yeah.net Xiaoping Zou, email: zouxiaopingmunj@163.com Keywords: colorectal cancer (CRC), protein kinase C ζ (PKCζ), AMP-activated protein kinase (AMPK), microRNA-25-5p, cell proliferation Received: March 08, 2017      Accepted: May 08, 2017      Published: June 27, 2017 ABSTRACT Developing novel strategies against human colorectal cancer (CRC) cells is needed. Activation of AMP-activated protein kinase (AMPK) could possibly inhibit CRC cells. Protein kinase C ζ (PKCζ) is an AMPK negative regulator. Here we found that PKCζ expression was significantly elevated in human colon cancer tissues and CRC cells. PKCζ upregulation was correlated with AMPK in-activation and mTOR complex 1 (mTORC1) over-activation. Reversely, PKCζ shRNA knockdown activated AMPK signaling and inhibited HT-29 cell proliferation. Significantly, downregulation of microRNA-25-5p (miR-25-5p), a PKCζ-targeting miRNA, could be the cause of PKCζ upregulation. Exogenous expression of miR-25-5p silenced PKCζ to activate AMPK signaling, which inhibited HT-29 cell proliferation. In vivo studies showed that HT-29 xenograft growth in mice was inhibited after expressing PKCζ shRNA or miR-25-5p. Collectively, PKCζ could be a novel oncogenic protein of human CRC. PKCζ silence, by targeted-shRNA or miR-25-5p expression, activates AMPK and inhibits HT-29 cell proliferation.