miR-133b suppresses metastasis by targeting HOXA9 in human colorectal cancer
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Xiao Wang1,*, Juyuan Bu1,*, Xingwei Liu1,*, Wenfeng Wang1, Weihua Mai2, Baojun Lv1, Jinlin Zou1, Xiangqiong Mo1, Xiaoling Li1, Jingyu Wang1, Bin Niu1, Yunping Fan3 and Bingzong Hou1
1Departments of General Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, China
2Departments of Preventive Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, China
3Departments 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
Bingzong Hou, email: [email protected]
Yunping Fan, email: [email protected]
Keywords: colorectal cancer, miR-133b, HOXA9, metastasis
Received: September 18, 2016 Accepted: June 11, 2017 Published: July 12, 2017
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.
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