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[Interaction between miR-21 and DNA methylation in different breast cancer cells]

Ying-yi Zhang, Wei-ping Tian, Mei Mei

    Zhongguo Ying Yong Sheng Li Xue Za Zhi = Zhongguo Yingyong Shenglixue Zazhi = Chinese Journal of Applied Physiology
    |September 22, 2015
    PubMed
    Abstract

    Insights

    MicroRNA-21 (miR-21) interacts with DNA methylation differently in breast cancer cells. Decreased DNA methylation upregulates miR-21, impacting cancer therapy development.

    Area of Science:

    • Molecular Biology
    • Cancer Research
    • Epigenetics

    Background:

    • MicroRNA-21 (miR-21) is implicated in various cancers, including breast cancer.
    • DNA methylation is a key epigenetic mechanism regulating gene expression.
    • The interplay between miR-21 and DNA methylation in breast cancer subtypes remains incompletely understood.

    Purpose of the Study:

    • To elucidate the interaction between miR-21 and DNA methylation in distinct breast cancer cell lines (MCF-7 and MDA-MB-231).
    • To investigate the regulatory effects of DNA methylation on miR-21 expression and its downstream targets.

    Main Methods:

    • Transfection of miR-21 inhibitors and negative controls into MCF-7 and MDA-MB-231 cells.
    • Assessment of miR-21 expression via real-time PCR.
    • Evaluation of genome-wide DNA methylation status using bisulfite-qMSP.
    • Treatment with 5-aza-2'-deoxycytidine (5-AZA) to modulate DNA methylation.
    • Western blot analysis to detect protein levels of PTEN and AKT.

    Main Results:

    • In MCF-7 cells, miR-21 inhibition led to decreased miR-21 expression and unregulated DNA methylation and DNMTs.
    • In MDA-MB-231 cells, miR-21 inhibition paradoxically increased miR-21 expression, alongside decreased genome-wide DNA methylation and altered DNMT expression (Dnmt3b downregulated, Dnmt3a upregulated).
    • 5-AZA treatment significantly increased miR-21 expression in both cell lines, elevated PTEN protein levels in MCF-7 cells, and influenced AKT signaling.

    Conclusions:

    • DNA methylation exhibits opposing regulatory effects on miR-21 in MCF-7 and MDA-MB-231 cells.
    • Decreased DNA methylation consistently upregulates miR-21 expression across both tested breast cancer cell lines.
    • Findings provide experimental evidence supporting the development of targeted therapies for diverse breast cancer subtypes based on miR-21 and DNA methylation interactions.

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