Wang Xiao, Bu Juyuan, Liu Xingwei, Wang Wenfeng, Mai Weihua, Lv Baojun, Zou Jinlin, Mo Xiangqiong, Li Xiaoling, Wang Jingyu, Niu Bin, Fan Yunping, Hou Bingzong
Departments of General Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, China.
Departments of Preventive Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, China.
Oncotarget. 2017 Jul 12;8(38):63935-63948. doi: 10.18632/oncotarget.19212. eCollection 2017 Sep 8.
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 and . 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.
微小RNA(miRNA)参与结直肠癌(CRC)转移的功能和机制在很大程度上尚不清楚。在此,对CRC原发组织和转移性肝组织进行了miRNA微阵列分析,以揭示参与CRC转移的关键miRNA。MiR-133b在CRC中表达降低且与转移呈负相关。MiR-133b的过表达显著抑制了CRC的转移。HOXA9被确定为miR-133b的直接功能性靶标。此外,HOXA9与miR-133b呈负相关并促进CRC的恶性进展。而且,miR-133b降低了HOXA9的表达,随后下调了ZEB1并上调了E-钙黏蛋白的表达。有趣的是,较低的miR-133b和较高的HOXA9表达显著导致CRC患者预后较差。多变量分析表明,miR-133b是CRC患者总生存的独立且重要的预测指标。总之,我们新确定miR-133b靶向HOXA9/ZEB1通路以促进CRC细胞中的肿瘤转移。该轴为miRNA调控CRC转移的机制提供了见解,并为CRC治疗提供了新的治疗靶点。