A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer
A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer
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DOI：
10.1038/s41388-018-0293-1
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发表时间：
2018-08-23
期刊：
影响因子：
8
通讯作者：
Lu, Pei-Jung
中科院分区：
文献类型：
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作者：
Wang, Po-Shun;Chou, Cheng-Han;Lu, Pei-Jung
三阴性乳腺癌(TNBC)患者常因转移而导致预后和生存期较差。TNBC转移的主要部位包括肺、脑、肝和骨。长非编码RNA(Long Non-Coding RNAs，LncRNAs)是长度超过200个核苷酸的非蛋白质编码转录本，已被报道为BC转移的重要调节因子。然而，lncRNAs调控TNBC转移的潜在机制尚不完全清楚。在此，我们发现Linc-ZNF469-3在肺转移的LM2-4175 TNBC细胞中高表达，并且过表达Linc-ZNF469-3增强了体外侵袭能力和干细胞特性以及体内肺转移。此外，我们还发现Linc-ZNF469-3与miR-574-5p存在物理上的相互作用，并且miR-574-5p的过表达抑制了ZEB1的表达。重要的是，内源性Linc-ZNF469-3和ZEB1的高表达与TNBC肺转移患者的肿瘤复发有关。综上所述，我们的研究结果提示Linc-ZNF469-3可能通过miR-574-5p-ZEB1信号轴促进TNBC的肺转移，可作为TNBC患者潜在的预后标志物。
Triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. The major sites for TNBC metastasis include the lungs, brain, liver, and bone. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides and have been reported as important regulators in BC metastasis. However, the underlying mechanisms for lncRNAs regulating TNBC metastasis are not fully understood. Here we found that linc-ZNF469-3 was highly expressed in lung-metastatic LM2-4175 TNBC cells and overexpression of linc-ZNF469-3 enhanced invasion ability and stemness properties in vitro and lung metastasis in vivo. Furthermore, we found linc-ZNF469-3 physically interacted with miR-574-5p and overexpression of miR-574-5p attenuated ZEB1 expression. Importantly, endogenous high expressions of linc-ZNF469-3 and ZEB1 were correlated with tumor recurrence in TNBC patients with lung metastasis. Taken together, our findings suggested that linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis and may be used as potential prognostic marker for TNBC patients.