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.

中文翻译：

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新型的长非编码RNA linc-ZNF469-3通过miR-574-5p-ZEB1轴促进三阴性乳腺癌中的肺转移。

三阴性乳腺癌（TNBC）患者通常由于转移而导致不良的预后和生存。TNBC转移的主要部位包括肺，脑，肝脏和骨骼。长的非编码RNA（lncRNA）是长于200个核苷酸的非蛋白质转录本，据报道是BC转移的重要调控因子。但是，尚未完全了解lncRNA调节TNBC转移的潜在机制。在这里，我们发现linc-ZNF469-3在肺转移性LM2-4175 TNBC细胞中高表达，并且linc-ZNF469-3的过表达增强了体外和体内肺转移的侵袭能力和干性。此外，我们发现linc-ZNF469-3与miR-574-5p发生了物理相互作用，miR-574-5p的过表达减弱了ZEB1的表达。重要的，Linc-ZNF469-3和ZEB1的内源性高表达与TNBC肺转移患者的肿瘤复发相关。综上所述，我们的发现表明linc-ZNF469-3可通过miR-574-5p-ZEB1信号轴促进TNBC的肺转移，并可作为TNBC患者的潜在预后标志物。