Upregulation of microRNA492 induced by epigenetic drug treatment inhibits the malignant phenotype of clear cell renal cell carcinoma in vitro

Author：

Publisher： Spandidos Publications

E-ISSN： 1791-3004|12|1|1413-1420

ISSN： 1791-2997

Source： Molecular Medicine Reports, Vol.12, Iss.1, 2015-01, pp. : 1413-1420

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Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer of the renal parenchyma. MicroRNAs (miRNAs) are noncoding RNAs of ~22 nucleotides in length, which function as posttranscriptional regulators. Recently, the downregulation of miRNA (miR)492 was observed to be associated with ccRCC; however, the molecular mechanism by which miR492 inhibited ccRCC remained to be elucidated. In the present study, it was demonstrated that miR492 was markedly downregulated in ccRCC tissues when compared with adjacent normal tissues, as determined by reverse transcriptionquantitative poymerase chain reaction (PCR). This downregulation was predominantly due to the hypermethylation of the CpG island of the miR492 promoter, which was detected by methylation specific PCR and bisulfite genomic sequencing PCR, and was shown to inhibit miR492 transcription. Through the use of a DNA demethylation agent, 5aza2'deoxycytidine or the histone deacetylase inhibitor 4phenylbutyric acid, the expression level of miR492 was significantly upregulated in ccRCC cells, which further inhibited cell proliferation and invasion, while promoting cell apoptosis and adhesion. In conclusion, the present study provided novel insights into the potential mechanisms involved in ccRCC and it is hypothesized that miR492 may become a promising therapeutic agent in the treatment of ccRCC.