miR-132 inhibits colorectal cancer invasion and metastasisviadirectly targeting ZEB2
Autor: | Gao-Chun Xiao, Yu Ding, Hai-Ping Luo, Qiang Shi, Yongbin Zheng, Zhi-Nan Hao, Shilun Tong, Qiu-Shuang Wang, Sheng-Bo Li |
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Rok vydání: | 2014 |
Předmět: |
Male
Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Colorectal cancer Kaplan-Meier Estimate Real-Time Polymerase Chain Reaction Cell Line Metastasis miR-132 Cell Line Tumor microRNA Humans Medicine Neoplasm Invasiveness Epithelial–mesenchymal transition Neoplasm Metastasis Survival analysis Aged Zinc Finger E-box Binding Homeobox 2 Homeodomain Proteins business.industry Gastroenterology General Medicine Middle Aged HCT116 Cells Prognosis medicine.disease digestive system diseases Gene Expression Regulation Neoplastic Repressor Proteins MicroRNAs HEK293 Cells Real-time polymerase chain reaction Disease Progression Cancer research Original Article Female Ectopic expression Colorectal Neoplasms business |
Zdroj: | World Journal of Gastroenterology. 20:6515 |
ISSN: | 1007-9327 |
Popis: | 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: | OpenAIRE |
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