title: miR-124 functions as a tumor suppressor in the endometrial carcinoma cell line HEC-1B partly by suppressing STAT3.
abstract: MicroRNAs (miRNAs) play an important role in the development and progression of endometrial carcinoma (EC). Recently, several studies have shown that microRNA-124 (miR-124) is downregulated in various cancers, which can affect tumor initiation and maintenance. However, the effects of miR-124 on EC are largely unknown. In this study, we identified the under-expression of miR-124 in 35 paired EC tissues and adjacent normal tissues. Further, functional experiments found that ectopic expression of miR-124 markedly suppressed cell proliferation, migration, and invasion of EC cells. It also induced cell apoptosis and G1-phase cell cycle arrest. Moreover, we identified signal transducer and activator of transcription 3 (STAT3) as a direct target of miR-124, and over expression of miR-124 not only induced changes in STAT3 expression but also altered expression of its target genes, cyclin D2 and matrix metalloproteinase 2, in the human endometrial carcinoma cell line HEC-1B. In addition to targeting STAT3 directly, we found that miR-124 suppresses phosphorylation of STAT3 through targeting IL-6R indirectly. Restored STAT3 expression through treatment with IL-6 cytokine partly abolished miR-124-mediated cell cycle arrest and apoptosis induction. These results combined with the tumorigenetic role of STAT3 in HEC-1B cells suggest that the antitumor effects of miR-124 are achieved, at least partly, through down regulation of STAT3 mRNA and its downstream target genes. Therefore, inhibition of constitutively activated STAT3 by ectopic expression of miR-124 in EC may provide a novel therapeutic strategy for the treatment of EC.
authors.affiliation: Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Li
authors.forename: Zhongzu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Huang
authors.forename: Wenfeng
authors.initials: W
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Kui
authors.initials: K
authors.lastname: Hong
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D056742:Cyclin D2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C080336:CCND2 protein, human; D056742:Cyclin D2; C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2