MiR-92a promotes stem cell-like properties by activating Wnt/β-catenin signaling in colorectal cancer

// Guang-Jun Zhang 1, 2, * , Li-Fa Li 1, 2, * , Guo-Dong Yang 3, * , Shu-Sen Xia 1 , Rong Wang 4 , Zheng-Wei Leng 2 , Zuo-Liang Liu 1 , Hong-Peng Tian 1 , Yi He 1 , Chang-Yuan Meng 1 , Dai-Zhi Liu 1 , Song-Lin Hou 1 , Xue-Gui Tang 5 and Tong Zhou 1, 2 1 The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China 2 Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan, China 3 Department of Gastroenterology, North Sichuan Medical College, Nanchong, Sichuan, China 4 Department of Gastrointestinal Surgery, The Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, China 5 Anorectal Department of Integrated Traditional Chinese and Western Medicine, North Sichuan Medical College, Nanchong, Sichuan, China * These authors have contributed equally to this work Correspondence to: Xue-Gui Tang, email: txg668nc@sohu.com Tong Zhou, email: zhoutong0088@163.com Keywords: colorectal cancer; miR-92a; stem cell; IL-6/STAT3; Wnt/β-catenin pathway Received: March 29, 2017     Accepted: September 18, 2017     Published: October 09, 2017 ABSTRACT We previously reported the oncogenic function of miR-92a in colorectal cancer. This study identified that miR-92a was upregulated in chemoresistant colorectal cancer cells and tissues. Ectopic expression of miR-92a conferred resistance to 5-fluorouracil-induced apoptosis in vitro , while antagomiR-92a significantly enhanced chemosensitivity in vivo . Moreover, Overexpression of miR-92a promoted the tumor sphere formation and the expression of stem cell markers. MiR-92a overexpression also displayed higher tumourigenesis in vivo . Furthermore, we demonstrated that miR-92a upregulates the Wnt/β-catenin signaling activity via directly targeting KLF4, GSK3β and DKK3, which are multiple level negative regulators of the Wnt/β-catenin signaling cascade. In addition, our results indicate IL-6/STAT3 pathway increases miR-92a expression by directly targeting its promoter, resulting in Wnt/β-catenin signaling activation and consequent promotion of stem-like phenotypes of colorectal cancer cells. Our present results suggest the essential role of IL-6/STAT3/miR-92a/Wnt/β-catenin pathway in regulating the stem cell-like traits of colorectal cancer cells and provide a potential target for colorectal cancer therapy.