Abstract
Breast cancer is the most common malignant disease amongst women. miRNAs are small, non-coding RNAs that regulate gene expression, thus have the potential to play an important role during cancer development. Emerging evidence shows that miR-135a is down-regulated in breast cancer cells, but the functional roles of miR-135a in breast cancer cells remains unexplored. For this purpose, we investigated the expression of miR-135a in breast cancer cells and explored its functional role during breast cancer progression. In vitro study showed that miR-135a may be a novel tumor suppressor. Further studies showed that transcription factors ELK1 and ELK3 are direct target genes of miR-135a that modulates the suppressive function of miR-135a in breast cancer cells. Induced expression of miR-135a significantly downregulated the expression of ELK1 and ELK3 both at mRNA and protein levels. Furthermore, the effect of miR-135a in MCF-7 and T47D cells was investigated by the overexpression of miR-135a mimics. In vitro, induced expression of miR-135a in breast cancer cells inhibited cell Proliferation and clongenicity. Moreover, a luciferase activity assay revealed that miR-135a could directly target the 3′-untranslated region (3′ UTRS) of ELK1 and ELK3 oncogenes. In addition, rescue experiment demonstrated that the promoted cell growth by transcription factors ELK1 and ELK3 was attenuated by the over-expression of miR-135a. Our study demonstrates that miR-135a regulates cell proliferation in breast cancer by targeting ELK1 and ELK3 oncogenes, and suggests that miR-135a potentially can act as a tumor suppressor.
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Acknowledgements
This work was supported by The National Key Scientific Programme of China (2016YFC1302305), The National Natural Science Foundation of China (81672609, 81472494, 81502282, 31671299). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Akhlaq Ahmad wishes to thank CAS-TWAS presidents PhD fellowship for the advancement of science in developing countries.
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Akhlaq Ahmad, Weijie Zhang, Mingming Wu, Sheng Tan and Tao Zhu declare that they have not any conflict of interest.
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This article does not contain any studies with human subjects or animals performed by any of the authors. All the experimental procedures were approved by Scientific Ethics Committee and Review Board of the School of Life Sciences, University of Science and Technology of China.
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Ahmad, A., Zhang, W., Wu, M. et al. Tumor-suppressive miRNA-135a inhibits breast cancer cell proliferation by targeting ELK1 and ELK3 oncogenes. Genes Genom 40, 243–251 (2018). https://doi.org/10.1007/s13258-017-0624-6
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DOI: https://doi.org/10.1007/s13258-017-0624-6