A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer

• Published in: Oncogene Vol. 37; no. 34; pp. 4662 - 4678
• Main Authors: Wang, Po-Shun, Chou, Cheng-Han, Lin, Cheng-Han, Yao, Yun-Chin, Cheng, Hui-Chuan, Li, Hao-Yi, Chuang, Yu-Chung, Yang, Chia-Ning, Ger, Luo-Ping, Chen, Yu-Chia, Lin, Forn-Chia, Shen, Tang-Long, Hsiao, Michael, Lu, Pei-Jung
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2018
• Subjects: Animals; Biomarkers, Tumor - genetics; Breast cancer; Cell Line, Tumor; Cell Movement - genetics; Female; Gene Expression Regulation, Neoplastic - genetics; Humans; Liver; Long bone; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lungs; MCF-7 Cells; Medical prognosis; Metastases; Metastasis; Mice; Mice, Inbred NOD; Mice, SCID; MicroRNAs - genetics; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Non-coding RNA; Nucleotides; RNA, Long Noncoding - genetics; Signal Transduction - genetics; Transcription Factors - genetics; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - pathology; Zinc Finger E-box-Binding Homeobox 1 - genetics
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-018-0293-1

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.