title: miR-132 inhibits colorectal cancer invasion and metastasis via directly targeting ZEB2.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our study indicated that miR-132 plays an important role in the invasion and metastasis of CRC.
authors.affiliation: 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.
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Hao
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.affiliation: 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.
authors.forename: Qiu-Shuang
authors.initials: QS
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Sheng-Bo
authors.initials: SB
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Gao-Chun
authors.initials: GC
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Shi-Lun
authors.initials: SL
authors.lastname: Tong
mesh_terms: D000368:Aged; D002460:Cell Line; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; C547077:MIRN132 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
keywords: Colorectal cancer; Epithelial-mesenchymal transition; Invasion; Metastasis; MicroRNA; Prognosis; miR-132