title: MiR-125a regulates ovarian cancer proliferation and invasion by repressing GALNT14 expression.
abstract: Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to tumor progression. The miR-125a was downregulated in several types of cancer, however, the molecular mechanism of miR-125a in the ovarian cancer remains unclear. The aim of the paper was to reveal the mechanism of miR-125a regulating cell proliferation and metastasis in ovarian cancer. In this study, western blotting, immunohistochemistry and serum-ELISA assay revealed that polypeptide N-acetylgalactosaminyl transferase 14 (GALNT14) expression was upregulated and correlated with the cancer stage in ovarian cancer. The expression levels of miR-125a were downregulated and negatively related to GALNT14 expression in clinical ovarian cancer tissues. Moreover, luciferase reporter assay identified polypeptide N-acetylgalactosaminyl transferase 14 (GALNT14) as a direct target of miR-125a, and overexpression of miR-125a markedly reduced the expression of GALNT14 in ovarian cancer. Functional characterization of miR-125a was accomplished by reconstitution of miR-125a and silencing GALNT14 expression in ovarian cancer cells to determine changes in proliferation and invasion. The MTT assay and transwell assay revealed that miR-125a transfectant significantly inhibits cell proliferation and invasion, by repressing GALNT14 expression. Furthermore, the gelatin zymography assay miR-125a mimics and GALNT14 siRNA suppressed the activity of MMP2 and MMP9. Taken together, our findings show that miR-125a functions as tumor suppressor in ovarian cancer by targeting GALNT14, and miR-125a may therefore serve as a biomarker for diagnosis and therapeutics in ovarian cancer.
authors.affiliation: Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central south University, Changsha 410078, Hunan, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Central south University, Changsha 410078, Hunan, PR China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central south University, Changsha 410078, Hunan, PR China. Electronic address: gy_li21@163.com.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005780:Gelatin / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D011485:Protein Binding / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D005780:Gelatin; D017350:N-Acetylgalactosaminyltransferases; C471038:UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 14, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: GALNT14; Invasion; Ovarian cancer; Proliferation; miR-125a