title: miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant cancers with high mortality around the world. However, the regulatory mechanism of ESCC carcinogenesis is not completely known. Here we demonstrate the novel role of miR-202 in regulating ESCC cell apoptosis. The analysis of data obtained from the GEO database showed that the expression of miR-202 is aberrantly decreased in tumor tissue from ESCC patients and cultured ESCC cell lines. After transfection with miR-202 mimic or inhibitor, the apoptotic capacity of ESCC cells was significantly increased by miR-202 overexpression but reduced by miR-202 repression. We then identified HSF2 as a direct target of miR-202 with the binding site on the 3'-UTR of HSF2 mRNA in ESCC cells. The apoptosis of ESCC cells induced by the miR-202 mimic could be repressed by HSF2 overexpression. Further studies indicated that HSF2 overexpression strongly upregulated the expression of Hsp70 at both the mRNA and protein levels. In addition, HSF2/Hsp70 suppressed ESCC cell apoptosis by preventing caspase 3 activation. In conclusion, miR-202 is a potential tumor suppressor in human ESCC and acts by regulating the apoptosis of ESCC cells by targeting HSF2, in which caspase 3 activation is involved. This might provide a novel therapeutic target for human ESCC.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Meng
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Lu
authors.forename: Wang
authors.initials: W
authors.lastname: Ma
authors.forename: Dongli
authors.initials: D
authors.lastname: Yue
authors.forename: Lijie
authors.initials: L
authors.lastname: Song
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Fan
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D018390:Gene Targeting / Q000379:methods; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D006360:Heat-Shock Proteins; C569392:MIRN202 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C070389:HSF2 protein, human