State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang Avenue, Nanjing 210004, Jiangsu, China.
Int J Mol Sci. 2019 Jul 24;20(15):3616. doi: 10.3390/ijms20153616.
Breast cancer, the most prevalent cancer type among women worldwide, remains incurable once metastatic. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in breast cancer by regulating specific genes or proteins. In this study, we found miR-133b was silenced in breast cancer cell lines and in breast cancer tissues, which predicted poor prognosis in breast cancer patients. We also confirmed that lncRNA NEAT1 was up-regulated in breast cancer and inhibited the expression of miR-133b, and identified the mitochondrial protein translocase of inner mitochondrial membrane 17 homolog A (TIMM17A) that serves as the target of miR-133b. Both miR-133b knockdown and TIMM17A overexpression in breast cancer cells promoted cell migration and invasion both in vitro and in vivo. In summary, our findings reveal that miR-133b plays a critical role in breast cancer cell metastasis by targeting TIMM17A. These findings may provide new insights into novel molecular therapeutic targets for breast cancer.
乳腺癌是全球女性最常见的癌症类型，一旦转移就无法治愈。长链非编码 RNA（lncRNA）和 microRNA（miRNA）通过调节特定的基因或蛋白质在乳腺癌中发挥重要作用。在这项研究中，我们发现 miR-133b 在乳腺癌细胞系和乳腺癌组织中被沉默，这预示着乳腺癌患者的预后不良。我们还证实，lncRNA NEAT1 在乳腺癌中上调，并抑制 miR-133b 的表达，并鉴定出作为 miR-133b 靶标的线粒体内膜转位酶 17 同源物 A（TIMM17A）。miR-133b 敲低和 TIMM17A 在乳腺癌细胞中的过表达均促进了细胞在体外和体内的迁移和侵袭。总之，我们的研究结果表明，miR-133b 通过靶向 TIMM17A 在乳腺癌细胞转移中发挥关键作用。这些发现可能为乳腺癌的新型分子治疗靶点提供新的见解。
