As an important epigenetic mechanism,histone acetylation modulates the transcription of many genes and plays important roles in hepatocellular carcinoma(HCC).Aberrations in histone acetylation have been observed in HC...
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As an important epigenetic mechanism,histone acetylation modulates the transcription of many genes and plays important roles in hepatocellular carcinoma(HCC).Aberrations in histone acetylation have been observed in HCC,but the factors that contribute to the aberrations have not been fully ***(miRNAs),which are noncoding RNAs that regulate gene expression,are involved in important epigenetic *** this study,we determined that the miR-200a and the level ofhistone H3 acetylation at its promoter were reduced in human HCC tissues in comparison with adjacent noncancerous hepatic ***,our results suggested that the histone deacetylase 4(HDAC4)inhibited the expression of miR-200a and its promoter activity and reduced the histone H3 acetylation level at the mir-200a promoter through a Sp1-dependent ***,we observed that the miR-200a directly targeted the 3'untranslated region of the HDAC4 mRNA and repressed HDAC4's ***,the miR-200a ultimately induced its own transcription and increased the histone H3 acetylation level at its own *** targeting HDAC4,the miR-200a also induced the upregulation of total acetyl-histone H3 levels and increased the histone H3 acetylation level at the p21WAF/Cip1 ***,we determined that the miR-200a inhibited the proliferation and migration of HCC cells in vivo and in ***:Our findings suggest that the HDAC4/Sp1/miR-200a regulatory network induces the downregulation of the miR-200a and the upregulation of HDAC4 in *** a consequence,the downregulation of the miR-200a enhances the proliferation and migration of the HCC cells and induces aberrant histone acetylation in *** findings highlight a potential therapeutic approach in targeting the HDAC4/Sp1/miR-200a regulatory network for the treatment of HCC.
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