4.5 Article

Upregulation of microRNA-492 induced by epigenetic drug treatment inhibits the malignant phenotype of clear cell renal cell carcinoma in vitro

Journal

MOLECULAR MEDICINE REPORTS
Volume 12, Issue 1, Pages 1413-1420

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2015.3550

Keywords

clear cell renal cell carcinoma; proliferation; apoptosis; microRNA-492; adhesion; invasion

Funding

  1. National Natural Science Foundation of China [81201672]
  2. Research Fund for the Doctoral Program of Guangdong Medical College [XB1331]
  3. Research Fund for the Doctoral Program of Affiliated Hospital of Guangdong Medical College [BK201208]

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Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer of the renal parenchyma. MicroRNAs (miRNAs) are non-coding RNAs of 22 nucleotides in length, which function as post-transcriptional regulators. Recently, the downregulation of miRNA (miR)-492 was observed to be associated with ccRCC; however, the molecular mechanism by which miR-492 inhibited ccRCC remained to be elucidated. In the present study, it was demonstrated that miR-492 was markedly downregulated in ccRCC tissues when compared with adjacent normal tissues, as determined by reverse transcription-quantitative poymerase chain reaction (PCR). This downregulation was predominantly due to the hypermethylation of the CpG island of the miR-492 promoter, which was detected by methylation specific PCR and bisulfite genomic sequencing PCR, and was shown to inhibit miR-492 transcription. Through the use of a DNA demethylation agent, 5-aza-2-deoxycytidine or the histone deacetylase inhibitor 4-phenylbutyric acid, the expression level of miR-492 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 miR-492 may become a promising therapeutic agent in the treatment of ccRCC.

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