Department of Emergency Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
Department of Cardio-Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
Kaohsiung J Med Sci. 2019 Aug;35(8):467-473. doi: 10.1002/kjm2.12085. Epub 2019 May 7.
MicroRNA-26a-5p (miR-26a-5p) has been reported to be involved in the tumorigenesis of several tumors, but its function in breast cancer is still unknown. In this study, miR-26a-5p was found significantly downregulated in both of the breast cancer tissues and cell lines, and low expression of miR-26a-5p predicted a poor prognosis for breast cancer patients. Overexpression of miR-26a-5p could significantly inhibit breast cancer cell growth. Further studies revealed that overexpression of miR-26a-5p downregulated the protein levels of Cyclin D1, CDK4, and CDK6, but upregulated the expression levels of p21, p27, and p53. In mechanism, miR-26a-5p targeted the 3'UTR of ring finger protein 6 (RNF6) mRNA and inhibited RNF6 expression in breast cancer cells. Moreover, overexpression of miR-26a-5p inhibited RNF6/ERα/Bcl-xL axis in breast cancer cells. In contrast, inhibiting miR-26a-5p upregulated RNF6/ERα/Bcl-xL axis. Further studies indicated that miR-26a-5p mediated RNF6/ERα/Bcl-xL axis through regulating the stability of ERα protein. Collectively, downregulation of miR-26a-5p plays essential roles in breast cancer by mediating RNF6/ERα/Bcl-xL axis, which might provide important implications for the therapeutics of breast cancer.
miR-26a-5p（miR-26a-5p）已被报道参与多种肿瘤的发生，但它在乳腺癌中的功能尚不清楚。在这项研究中，发现 miR-26a-5p 在乳腺癌组织和细胞系中均显著下调，miR-26a-5p 低表达预示着乳腺癌患者预后不良。过表达 miR-26a-5p 可显著抑制乳腺癌细胞生长。进一步的研究表明，过表达 miR-26a-5p 下调了 Cyclin D1、CDK4 和 CDK6 的蛋白水平，但上调了 p21、p27 和 p53 的表达水平。在机制上，miR-26a-5p 靶向环指蛋白 6（RNF6）mRNA 的 3'UTR 并抑制乳腺癌细胞中的 RNF6 表达。此外，过表达 miR-26a-5p 抑制了乳腺癌细胞中的 RNF6/ERα/Bcl-xL 轴。相反，抑制 miR-26a-5p 上调了 RNF6/ERα/Bcl-xL 轴。进一步的研究表明，miR-26a-5p 通过调节 ERα 蛋白的稳定性来介导 RNF6/ERα/Bcl-xL 轴。总之，miR-26a-5p 的下调通过介导 RNF6/ERα/Bcl-xL 轴在乳腺癌中发挥重要作用，这可能为乳腺癌的治疗提供重要意义。
