Linc-ZNF469-3 enhances lung metastasis through regulating miR-574-5p/ZEB1 in triple negative breast cancer

• Main Authors: Cheng-HanChou, 周承翰
• Other Authors: Pei-Jung Lu
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/41598159557569862356

碩士 === 國立成功大學 === 臨床醫學研究所 === 104 === Distant metastasis is a leading cause of death in cancers. The lung, liver, brain, and bone are frequent metastatic sites of breast cancer. The underlying mechanism of breast cancer cells with tissue specific tropism remains unclear. Long noncoding RNAs are defined as transcripts longer than 200 nucleotides that lack protein coding potential and enable to regulate tumor progression. We hypothesized that long noncoding RNAs can mediate the lung tropism in breast cancer. According to Next Generation Sequencing (NGS) data, linc-ZNF469-3 was identified as a lung tropism related lncRNA from lung specific metastatic breast cancer cells. Our results showed that overexpression of linc-ZNF469-3 can increase ZEB1 protein level and metastatic ability in vitro. In addition, linc-ZNF469-3 stably expressing cells can increase lung metastasis ability compared with control group in xenograft mice model. MiR-574-5p was then identified as linc-ZNF469-3 targeting miRNA. We demonstrated that linc-ZNF469-3 may function as a sponge for sequestering miR-574-5p from targeting and down-regulating ZEB1. Furthermore, high linc-ZNF469-3 alone or combined with high ZEB1 is correlated with lung recurrence in triple negative breast cancer patients. The conclusion of the current study is that linc-ZNF469-3 increases lung metastasis ability in breast cancer may through mediating miR-574-5p-ZEB1 pathway. Taken together, our results demonstrate that linc-ZNF469-3 can serve as potential diagnostic and prognostic markers for TNBC lung recurrence patients.