miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPβ

// Xiao-Fei Zhang 1 , Ke-ke Li 1 , Lu Gao 3 , Shang-Ze Li 1 , Ke Chen 4 , Jun-Bin Zhang 5 , Di Wang 6 , Rong-Fu Tu 1 , Jin-Xiang Zhang 2 , Kai-Xiong Tao 2 , Guobin Wang 2, * , Xiao-Dong Zhang 1, * 1 College of Life Sciences, Wuhan University, Wuhan 430072, PR China 2 Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, PR China 3 Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, PR China 4 Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, PR China 5 Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, PR China 6 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, PR China * These authors have contributed equally to this work Correspondence to: Xiao-Dong Zhang, e-mail: zhangxd@whu.edu.cn Keywords: microRNA-191, colorectal cancer, apoptosis, C/EBPβ, tumorigenesis Received: August 28, 2014      Accepted: December 07, 2014      Published: December 27, 2014 ABSTRACT MicroRNA-191 (miR-191), a small non-coding RNA, is involved in disease development and cancer diagnosis and prognosis. However, how miR-191 functions in colorectal cancer remains largely unclear. In this study, we show that miR-191 is highly expressed in colon tumor tissues, and that inhibition of miR-191 leads to decreased cell growth, proliferation and tumorigenicity in a xenograft model. Overexpression of miR-191 in colorectal cancer cell lines alters cell cycle progression and cell resistance to 5-Fu induced cell apoptosis. Mechanistic studies demonstrated that miR-191 directly binds to the 3’UTR of the C/EBPβ mRNA and mediates a decrease in the mRNA and protein expression of C/EBPβ. We further showed that C/EBPβ induces growth arrest in a colorectal cancer cell line and that its expression is negatively correlated with the miR-191 level in patient samples. Our findings suggest that miR-191 may be a potential gene therapy target for the treatment of colorectal cancer.