Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Gene. 2014 Feb 10;535(2):191-7. doi: 10.1016/j.gene.2013.11.035. Epub 2013 Dec 4.
MicroRNAs (miRNAs) are strongly implicated in many cancers, including breast cancer. Recently, microRNA-301a (miR-301a) has been proved to play a substantial role in gastric cancer, but its functions in the context of breast cancer remain unknown. Here we report that miR-301a was markedly upregulated in primary tumor samples from patients with distant metastases and pro-metastatic breast cancer cell lines. Gain-of-function and loss-of-function studies showed that ectopic overexpression of miR-301a promoted breast cancer cell migration, invasion and metastasis both in vitro and in vivo. Notably, Wnt/β-catenin signaling was hyperactivated in metastatic breast cancer cells that express miR-301a, and mediated miR-301a-induced invasion and metastasis. Furthermore, miR-301a directly targeted and suppressed PTEN, one negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that miR-301a maintains constitutively activated Wnt/β-catenin signaling by directly targeting PTEN, which promotes breast cancer invasion and metastasis. Taken together, our findings reveal a new regulatory mechanism of miR-301a and suggest that miR-301a might be a potential target in breast cancer therapy.
微小 RNA（miRNAs）在多种癌症中起重要作用，包括乳腺癌。最近，miR-301a（miR-301a）已被证明在胃癌中发挥重要作用，但在乳腺癌中的作用尚不清楚。在这里，我们报告miR-301a 在具有远处转移和促转移乳腺癌细胞系的患者的原发性肿瘤样本中明显上调。功能获得和功能丧失研究表明，miR-301a 的异位过表达促进了体外和体内乳腺癌细胞的迁移、侵袭和转移。值得注意的是，在表达 miR-301a 的转移性乳腺癌细胞中，Wnt/β-catenin 信号通路被过度激活，并介导了 miR-301a 诱导的侵袭和转移。此外，miR-301a 直接靶向并抑制了 Wnt/β-catenin 信号通路的负调节因子 PTEN。这些结果表明，miR-301a 通过直接靶向 PTEN 来维持 Wnt/β-catenin 信号的持续激活，从而促进乳腺癌的侵袭和转移。总之，我们的研究结果揭示了 miR-301a 的新调控机制，并表明 miR-301a 可能是乳腺癌治疗的潜在靶点。
