miR-132 inhibits colorectal cancer invasion and metastasis via directly targeting ZEB2.

Autor: Zheng YB; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China., Luo HP; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China., Shi Q; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China., Hao ZN; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China., Ding Y; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China., Wang QS; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China., Li SB; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China., Xiao GC; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China., Tong SL; Yong-Bin Zheng, Hai-Ping Luo, Qiang Shi, Zhi-Nan Hao, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Gao-Chun Xiao, Shi-Lun Tong, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Jazyk: angličtina
Zdroj: World journal of gastroenterology [World J Gastroenterol] 2014 Jun 07; Vol. 20 (21), pp. 6515-22.
DOI: 10.3748/wjg.v20.i21.6515
Abstrakt: Aim: To investigate the biological role and underlying mechanism of miR-132 in colorectal cancer (CRC) progression and invasion.
Methods: Quantitative RT-PCR analysis was used to examine the expression levels of miR-132 in five CRC cell lines (SW480, SW620, HCT116, HT29 and LoVo) and a normal colonic cell line NCM460, as well as in tumor tissues with or without metastases. The Kaplan-Meier method was used to analyze the prognostic significance of miR-132 in CRC patients. The biological effects of miR-132 were assessed in CRC cell lines using the transwell assay. Quantitative RT-PCR and western blot analyses were employed to evaluate the expression of miR-132 targets. The regulation of ZEB2 by miR-132 was confirmed using the luciferase activity assay.
Results: miR-132 was significantly down-regulated in the CRC cell lines compared with the normal colonic cell line (P < 0.05), as well as in the CRC tissues with distant metastases compared with the tissues without metastases (10.52 ± 4.69 vs 23.11 ± 7.84) (P < 0.001). Down-regulation of miR-132 was associated with tumor size (P = 0.016), distant metastasis (P = 0.002), and TNM stage (P = 0.020) in CRC patients. Kaplan-Meier survival curve analysis indicated that patients with low expression of miR-132 tended to have worse disease-free survival than patients with high expression of miR-132 (P < 0.001). Moreover, ectopic expression of miR-132 markedly inhibited cell invasion (P < 0.05) and the epithelial-mesenchymal transition (EMT) in CRC cell lines. Further investigation revealed ZEB2, an EMT regulator, was a downstream target of miR-132.
Conclusion: Our study indicated that miR-132 plays an important role in the invasion and metastasis of CRC.
Databáze: MEDLINE