title: MicroRNA-218 inhibits the proliferation and metastasis of esophageal squamous cell carcinoma cells by targeting BMI1.
abstract: MicroRNAs (miRNAs or miRs) play a pivotal role in esophageal carcinogenesis either as oncogenes or as tumor suppressor genes. In the present study, we found that the expression level of miR-218 was significantly reduced in esophageal squamous cell carcinoma (ESCC) tissues and ESCC cell lines. Moreover, its expression was found to correlate with the clinicopathological stage of ESCC; miR-218 expression was lower in the stage III tissue samples than in the stage I and II tissue samples. Furthermore, the decreased expression of miR-218 was found to be associated with an enhanced ESCC cell proliferation and metastasis. Western blot analysis and luciferase reporter assay revealed that miR-218 decreased BMI1 expression by binding to the putative binding sites in its 3'-untranslated region (3'-UTR). The BMI1 mRNA expression levels were markedly increased and negatively correlated with the miR-218 expression level in the ESCC tissues. Functional analyses revealed that the restoration of miR-218 expression inhibited ESCC cell proliferation, migration and invasion and promoted apoptosis. The knockdown of BMI1 by siRNA showed the same phenocopy as the effect of miR-218 on ESCC cells, indicating that BMI1 was a major target of miR-218. In the present study, our findings confirm miR-218 as a tumor suppressor and identify BMI1 as a novel target of miR-218 in ESCC. Therefore, miR-218 may prove to be a useful biomarker for monitoring the initiation and development of ESCC, and may thus be an effective therapeutic target in ESCC.
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000166:cytology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7