The miR-124-p63 feedback loop modulates colorectal cancer growth

// Kuijie Liu 1 , Hongliang Yao 1 , Sanlin Lei 1 , Li Xiong 1 , Haizhi Qi 1 , Ke Qian 1 , Jiqiang Liu 1 , Peng Wang 1 , Hua Zhao 1 1 Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China Correspondence to: Hua Zhao, email: drzhaohua2012@163.com Keywords: miR-124, p63, feedback loop, cell growth, colorectal cancer Received: May 26, 2016      Accepted: February 20, 2017      Published: March 16, 2017 ABSTRACT Among the diverse co-regulatory relationships between transcription factors (TFs) and microRNAs (miRNAs), feedback loops have received the most extensive research attention. The co-regulation of TFs and miRNAs plays an important role in colorectal cancer (CRC) growth. Here, we show that miR-124 can regulate two isoforms of p63, TAp63 and ΔNp63, via iASPP, while p63 modulates signal transducers and activators of transcription 1 (STAT1) expression by targeting miR-155. Moreover, STAT1 acts as a regulator of CRC growth by targeting miR-124. Taken together, these results reveal a feedback loop between miRNAs and TFs. This feedback loop comprises miR-124, iASPP, STAT1, miR-155, TAp63 and ΔNp63, which are essential for CRC growth. Moreover, this feedback loop is perturbed in human colon carcinomas, which suggests that the manipulation of this microRNA-TF feedback loop has therapeutic potential for CRC.