miR-125b inhibited epithelial-mesenchymal transition of triple-negative breast cancer by targeting MAP2K7.
miR-125b inhibited epithelial-mesenchymal transition of triple-negative breast cancer by targeting MAP2K7.
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DOI：
10.2147/ott.s102713
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发表时间：
2016
影响因子：
4
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Hong L;Pan F;Jiang H;Zhang L;Liu Y;Cai C;Hua C;Luo X;Sun J;Chen Z
MicroRNA (miRNA) 在多种生物过程中发挥着重要作用，并且正在成为肿瘤发生和肿瘤进展的关键调节因子。在乳腺癌差异表达的 miRNA 中，miR-125b 被发现失调，与三阴性乳腺癌 (TNBC) 的不良预后和化疗耐药相关，但其机制仍不清楚。在我们的研究中，我们发现 TNBC 组织中 miR-125b 的表达下调，表达 miR-125b 的 Hs578T 细胞的迁移和侵袭减少。随后检测到 MAP2K7 是 miR-125b 的新靶点，并且 miR-125b 对 MAP2K7 的下调类似于 MAP2K7 的短暂敲低，从而阻碍 Hs578T 细胞的上皮间质转化（EMT）。 miR-125b 过表达的 Hs578T 细胞中 MAP2K7 的上调部分挽救了 miR-125b 的迁移和侵袭抑制。此外，与正常组织相比，MAP2K7 在 TNBC 样本中过表达，并且与 miR-125b 表达呈负相关。鉴于这些发现，miR-125b 通过靶向 MAP2K7 抑制 EMT，成为 TNBC 中的肿瘤抑制因子。
MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. Among the differentially expressed miRNAs in breast cancer, miR-125b was revealed to be deregulated and associated with poor prognosis and chemoresistance in triple-negative breast cancer (TNBC), but the mechanism is still unknown. In our study, we showed downregulated expression of miR-125b in TNBC tissues and decreased migration and invasion in miR-125b-expressing Hs578T cells. MAP2K7 was then detected to be a novel target of miR-125b, and downregulation of MAP2K7 by miR-125b was similar to transient knockdown of MAP2K7 which hindered epithelial–mesenchymal transition (EMT) of Hs578T cells. Upregulation of MAP2K7 in miR-125b-overexpressing Hs578T cells partly rescued the migration and invasion suppression of miR-125b. Furthermore, MAP2K7 was overexpressed in TNBC samples compared with normal tissues and negatively correlated with miR-125b expression. In light of these findings, miR-125b emerged as a tumor suppressor in TNBC by targeting MAP2K7 to inhibit EMT.