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MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells

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Tumor Biology

Abstract

MicroRNAs (miRNAs) are small non-protein-coding RNAs that regulate expression of a wide variety of genes including those involved in cancer development. Here, we investigate the role of miR-143 in breast cancer. In this study, we showed that miR-143 was frequently downregulated in 80 % of breast carcinoma tissues compared to their adjacent noncancerous tissues. Ectopic expression of miR-143 inhibited proliferation and soft agar colony formation of breast cancer cells and also downregulated DNA methyltransferase 3A (DNMT3A) expression on both mRNA and protein levels. Restoration of miR-143 expression in breast cancer cells reduces PTEN hypermethylation and increases TNFRSF10C methylation. DNMT3A was demonstrated to be a direct target of miR-143 by luciferase reporter assay. Furthermore, miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in breast cancer tissues. Our findings suggest that miR-143 regulates DNMT3A in breast cancer cells. These findings elucidated a tumor-suppressive role of miR-143 in epigenetic aberration of breast cancer, providing a potential development of miRNA-based treatment for breast cancer.

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Abbreviations

miRNA:

microRNA

DNMT:

DNA methyltransferase

qRT-PCR:

Quantitative reverse transcription–polymerase chain reaction

3′UTR:

3′ Untranslated region

MTT:

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

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Correspondence to Ava Kwong.

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Ng, E.K.O., Li, R., Shin, V.Y. et al. MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells. Tumor Biol. 35, 2591–2598 (2014). https://doi.org/10.1007/s13277-013-1341-7

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  • DOI: https://doi.org/10.1007/s13277-013-1341-7

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