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Hypermethylated miR-424 in Colorectal Cancer Subsequently Upregulates VEGF

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Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

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.

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Funding

This work was supported by (95-03-30-32977) from the Deputy of Research, Tehran University of Medical Sciences.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Zahra Nouri Ghonbalani, Shiva Shahmohamadnejad, Parvin Pasalar & Ehsan Khalili

Authors
  1. Zahra Nouri Ghonbalani
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  2. Shiva Shahmohamadnejad
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  3. Parvin Pasalar
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  4. Ehsan Khalili
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Contributions

EK and PP: concept, ideas, and writing. ZNGH and SHSH: performed experiments and biostatistics. All authors have read and agree with this paper.

Corresponding author

Correspondence to Ehsan Khalili.

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Ethics Statement

This work complies with the guidelines of the World Medical Association, Declaration of Helsinki. This work was approved by the Human Research Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.MEDICINE.REC.1395.997).

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The authors declare that they have no conflict of interest.

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Ghonbalani, Z.N., Shahmohamadnejad, S., Pasalar, P. et al. Hypermethylated miR-424 in Colorectal Cancer Subsequently Upregulates VEGF. J Gastrointest Canc 53, 380–386 (2022). https://doi.org/10.1007/s12029-021-00614-0

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  • DOI: https://doi.org/10.1007/s12029-021-00614-0

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