miR-133b suppresses metastasis by targeting HOXA9 in human colorectal cancer

Abstract

// Xiao Wang 1, * , Juyuan Bu 1, * , Xingwei Liu 1, * , Wenfeng Wang 1 , Weihua Mai 2 , Baojun Lv 1 , Jinlin Zou 1 , Xiangqiong Mo 1 , Xiaoling Li 1 , Jingyu Wang 1 , Bin Niu 1 , Yunping Fan 3 and Bingzong Hou 1 1 Departments of General Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, China 2 Departments of Preventive Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, China 3 Departments of ENT - Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, China * These authors contributed equally to this work and should be considered co-first authors Correspondence to: Bingzong Hou, email: houbingzong@126.com Yunping Fan, email: zhfanyp@163.com Keywords: colorectal cancer, miR-133b, HOXA9, metastasis Received: September 18, 2016 Accepted: June 11, 2017 Published: July 12, 2017 ABSTRACT Functions and mechanisms of microRNA (miRNA) involved in colorectal cancer (CRC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in CRC primary tissues and metastatic hepatic tissues to disclose crucial miRNA involved in CRC metastasis. MiR-133b was decreased and negatively correlated with metastasis in CRC. Overexpression of miR-133b significantly suppressed metastasis of CRC in vitro and in vivo . HOXA9 was identified as a direct and functional target of miR-133b. In addition, HOXA9 was negatively correlated with miR-133b and promoted CRC malignant progress. Moreover, miR-133b decreased HOXA9 expression, and subsequently downregulated ZEB1 and upregulated E-cadherin expression. Intriguingly, lower miR-133b and higher HOXA9 expression significantly contributed to poorer outcomes in CRC patients. Multivariate analysis indicated that miR-133b was an independent and significant predictor of CRC patient overall survival. In conclusion, we newly determined that miR-133b targeted the HOXA9/ZEB1 pathway to promote tumor metastasis in CRC cells. This axis provided insights into the mechanism underlying miRNA regulation of CRC metastasis and a novel therapeutic target for CRC treatment.