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Apoptosis-inducing and antiproliferative effect by inhibition of miR-182-5p through the regulation of CASP9 expression in human breast cancer

Cancer Gene Therapy volume 24, pages 75–82 (2017)Cite this article

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Abstract

Recent advances in molecular medicine and gene therapy have offered new effective achievements in the treatment of cancers. One of the molecular research lines for the diagnosis and treatment of cancer is the use of microRNAs (miRNAs), which are single-stranded noncoding RNAs. miRNAs are involved in the post-transcriptional regulation of gene expression and have a role in the growth, differentiation, cell death and cancer development. One of the miRNAs that showed upregulation in breast cancer is miR-182-5p. Oncogenic features of miR-182-5p in some cancers were confirmed. In the present study, blockage of miR-182-5p was performed in human breast cancer cell line (MCF-7) using locked nucleic acid (LNA)-anti-miR. MTT (3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay and annexin/propidium iodide staining at different time points after LNA-anti-miR-182-5p transfection were accomplished. Our results showed that miR-182-5p inhibition can reduce the viability of MCF-7 cells because of apoptosis induction, probably through the upregulation of CASP9. A western blot analysis revealed that the expression of CASP9 protein is associated with miR-182-5p inhibition. The CASP9 protein acts as an initiator caspase of apoptosis in the mitochondrial cell death pathway. Our results can be used in translational medicine for future investigation in breast cancer and approach treatment based on antisense therapy.

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Acknowledgements

This study was conducted with the support of Isfahan University of Medical Sciences (IRAN) with grant number 194113. This study was approved by the local ethics committee of Isfahan University of Medical Sciences (IRAN) and the studies have been approved by the appropriate institutional and/or a national research ethics committee and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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  1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran

    M Sharifi & A Moridnia

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Correspondence to M Sharifi.

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Sharifi, M., Moridnia, A. Apoptosis-inducing and antiproliferative effect by inhibition of miR-182-5p through the regulation of CASP9 expression in human breast cancer. Cancer Gene Ther 24, 75–82 (2017). https://doi.org/10.1038/cgt.2016.79

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