MiR-92a promotes stem cell-like properties by activating Wnt/β-catenin signaling in colorectal cancer
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Guang-Jun Zhang1,2,*, Li-Fa Li1,2,*, Guo-Dong Yang3,*, Shu-Sen Xia1, Rong Wang4, Zheng-Wei Leng2, Zuo-Liang Liu1, Hong-Peng Tian1, Yi He1, Chang-Yuan Meng1, Dai-Zhi Liu1, Song-Lin Hou1, Xue-Gui Tang5 and Tong Zhou1,2
1The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
2Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan, China
3Department of Gastroenterology, North Sichuan Medical College, Nanchong, Sichuan, China
4Department of Gastrointestinal Surgery, The Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, China
5Anorectal Department of Integrated Traditional Chinese and Western Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
*These authors have contributed equally to this work
Xue-Gui Tang, email: firstname.lastname@example.org
Tong Zhou, email: email@example.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
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.
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