Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Aug 5;51(8):791-798. doi: 10.1093/abbs/gmz067.
MicroRNAs (miRNAs) are a class of endogenous noncoding genes that regulate gene expression at the posttranscriptional level. In recent decades, miRNAs have been reported to play important roles in tumor growth and metastasis, while some reported functions of a specific miRNA in tumorigenesis are contradictory. In this study, we reevaluated the role of miR-214, which has been reported to serve as an oncogene or anti-oncogene in breast cancer metastasis. We found that miR-214 inhibited breast cancer via targeting RNF8, a newly identified regulator that could promote epithelial-mesenchymal transition (EMT). Specifically, the survival rate of breast cancer patients was positively correlated with miR-214 levels and negatively correlated with RNF8 expression. The overexpression of miR-214 inhibited cell proliferation and invasion of breast cancer, while suppression of miR-214 by chemically modified antagomir enhanced the proliferation and invasion of breast cancer cells. Furthermore, miR-214 could modulate the EMT process via downregulating RNF8. To our knowledge, this is the first report that reveals the role of the miR-214-RNF8 axis in EMT, and our results demonstrate a novel mechanism for miR-214 acting as a tumor suppressor through the regulation of EMT.
微小 RNA（miRNA）是一类内源性非编码基因，可在转录后水平调节基因表达。近几十年来，已有研究报道 miRNAs 在肿瘤生长和转移中发挥重要作用，而某些特定 miRNA 在肿瘤发生中的作用则相互矛盾。在这项研究中，我们重新评估了 miR-214 的作用，已有研究报道 miR-214 可作为乳腺癌转移的癌基因或抑癌基因。我们发现 miR-214 通过靶向 RNF8 抑制乳腺癌，RNF8 是一种新发现的可促进上皮-间充质转化（EMT）的调控因子。具体而言，乳腺癌患者的生存率与 miR-214 水平呈正相关，与 RNF8 表达呈负相关。miR-214 的过表达抑制了乳腺癌细胞的增殖和侵袭，而通过化学修饰的反义寡核苷酸抑制 miR-214 的表达则增强了乳腺癌细胞的增殖和侵袭。此外，miR-214 可通过下调 RNF8 来调节 EMT 过程。据我们所知，这是首次报道 miR-214-RNF8 轴在 EMT 中的作用，我们的研究结果表明 miR-214 通过调节 EMT 作为肿瘤抑制因子的一种新机制。
