Ahmad Akhlaq, Zhang Weijie, Wu Mingming, Tan Sheng, Zhu Tao
Laboratory of Molecular Tumor Pathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, 230027, Anhui, People's Republic of China.
Genes Genomics. 2018 Mar;40(3):243-251. doi: 10.1007/s13258-017-0624-6. Epub 2017 Oct 19.
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.
乳腺癌是女性中最常见的恶性疾病。微小RNA（miRNAs）是一类小的非编码RNA，可调节基因表达，因此在癌症发展过程中可能发挥重要作用。新出现的证据表明，miR-135a在乳腺癌细胞中表达下调，但其在乳腺癌细胞中的功能作用仍未得到探索。为此，我们研究了miR-135a在乳腺癌细胞中的表达，并探讨了其在乳腺癌进展过程中的功能作用。体外研究表明，miR-135a可能是一种新型肿瘤抑制因子。进一步研究表明，转录因子ELK1和ELK3是miR-135a的直接靶基因，它们调节miR-135a在乳腺癌细胞中的抑制功能。miR-135a的诱导表达在mRNA和蛋白质水平上均显著下调ELK1和ELK3的表达。此外，通过过表达miR-135a模拟物研究了miR-135a在MCF-7和T47D细胞中的作用。在体外，miR-135a在乳腺癌细胞中的诱导表达抑制了细胞增殖和克隆形成能力。此外，荧光素酶活性测定表明，miR-135a可直接靶向ELK1和ELK3癌基因的3'-非翻译区（3'UTR）。此外，挽救实验表明，转录因子ELK1和ELK3促进的细胞生长被miR-135a的过表达所减弱。我们的研究表明，miR-135a通过靶向ELK1和ELK3癌基因调节乳腺癌细胞增殖，并提示miR-135a可能作为一种肿瘤抑制因子发挥作用。
