MiR-125 a suppresses ovarian cancer proliferation and motility by targeting HDAC 4

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2016)

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摘要
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 study the expression of miR-125a in ovarian cancer and miR-125a’s relation to the cell proliferation and invasion in ovarian cancer. In this study, we demonstrated that miR-125a is downregulated in ovarian cancer tissues and cell lines, compared with the corresponding adjacent non-neoplastic tissues and normal human fallopian tube epithelial cell line. Histone deacetylase 4 (HDAC4), which has been reported to be associated with invasive ovarian cancer, was identified as a novel target of miR-125a in OVCAR-3 ovarian cancer cells, and the protein expression of HDAC4 was negatively regulated by miR-125a in OVCAR-3 cells. Additionally, upregulation of miR-125a and downregulation of HDAC4 suppressed ovarian cancer cell proliferation and invasion. These data suggest that miR-125a may suppress ovarian cancer cell proliferation and invasion through direct inhibition of HDAC4 expression. Taken together, our findings show that miR125a functions as tumor suppressor in ovarian cancer by targeting HDAC4, and miR-125a may therefore serve as a biomarker for diagnosis and therapeutics in ovarian cancer.
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关键词
miR-125a, HDAC4, ovarian cancer, proliferation, invasion
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