Hypermethylated miR-424 in Colorectal Cancer Subsequently Upregulates VEGF

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Abstract
Purpose Colorectal cancer (CRC) is the second leading cause of death from cancer in adults. Recent advances have shown that cancer cells can have some epigenetic changes involved in all stages of cancer. It has also been shown that miR-424 acts as gene expression regulators in many biological processes, including angiogenesis with mediators such as VEGF. In the current study, to identify the potential role of miR-424 in colorectal cancer progression, methylation status of miR-424 promoter region and its expression level have been evaluated. Besides, the correlation between VEGF level and miR-424 expression level has been assessed. Methods Methylation status miR-424 promoter was assessed using methylation-specific polymerase chain reaction (MSP). The expression level of miR-424 in human colorectal cancer tissue was analyzed by quantitative PCR. HCT116 cell line was selected to evaluate the correlation between the miR-424 expression level and the promoter’s methylation status. VEGF expression, one out of mir-424 targets involved in angiogenesis and cancer progression, was measured by western blot analysis in the pairs of cancer tissues and their adjacent tissues. Results Our results have revealed that the promoter region of miR-424 is methylated in cancer cells compared to normal cells, leading to downregulation of miR-424 in the colorectal cancer tissues compared to the normal tissues. Also, we found that the expression protein’s level of VEGF in the tumor cells is increased compared with normal tissues. Conclusion The present study suggests that hypermethylation downregulates miR-424. VEGF expression is upregulated with decreased miR-424 in colorectal cancer, which results in cancer progression.
Funding Information
  • Tehran University of Medical Sciences and Health Services (95-03-30-32977)

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