Qi Lu1, Li Wang2,3, Yabiao Gao1, Ping Zhu1, Luying Li1, Xue Wang1, Youping Jin1, Xiuling Zhi1, Jerry Yu4, Xin Li5, Xingjun Qin6, Ping Zhou7. 1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130 Dong'an Road, Shanghai, 200032, China. 2. Institutes of Biomedical Sciences, Fudan University, No. 130 Dong'an Road, Shanghai, 200032, China. 3. Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, China. 4. Department of Medicine, University of Louisville, Louisville, KY, 40292, USA. 5. Department of Oral & Maxillofacial - Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhi Zao Ju Road, Shanghai, 200011, China. 6. Department of Oral & Maxillofacial - Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhi Zao Ju Road, Shanghai, 200011, China. qinxj1989@sina.com. 7. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, No. 130 Dong'an Road, Shanghai, 200032, China. zping@shmu.edu.cn.
Abstract
BACKGROUND: Anoikis resistance plays a critical role in the tumor metastasis by allowing survival of cancer cells in the systemic circulation. We previously showed that long non-coding RNAs APOC1P1-3 (lncRNA APOC1P1-3) inhibit apoptosis of breast cancer cells. In this study, we explored its role in anoikis resistance. METHODS: We induced anoikis resistance in two breast cancer cell lines (MCF-7 and MDA-MB-231) under anchorage-independent culture conditions and studied lncRNA APOC1P1-3 effects on apoptosis. Using Dual-Luciferase activity assay, we determined whether it specifically binds to miRNA-188-3P. We further explored its role in lung metastasis by injecting MDA-MB-231 and MDA-MB-231-APOC1P1-3-knock-down cells in female BALB/c nude mice. RESULTS: We found that lncRNA APOC1P1-3 suppressed early apoptosis of these cells (demonstrated by gain or loss of their function, respectively) and promoted anoikis resistance via reducing activated- Caspase 3, 8, 9 and PARP. Moreover, it specifically binds to the target miRNA-188-3p acting as a "sponge" to block the inhibition of Bcl-2 (an anti-apoptosis protein). CONCLUSIONS: Our study supports a theory that lncRNA APOC1P1-3 can promote development of breast cancer metastasis via anoikis resistance by specifically binding to miRNA-188-3p to block the inhibition of Bcl-2.
BACKGROUND: Anoikis resistance plays a critical role in the tumor metastasis by allowing survival of cancer cells in the systemic circulation. We previously showed that long non-coding RNAs APOC1P1-3 (lncRNA APOC1P1-3) inhibit apoptosis of breast cancer cells. In this study, we explored its role in anoikis resistance. METHODS: We induced anoikis resistance in two breast cancer cell lines (MCF-7 and MDA-MB-231) under anchorage-independent culture conditions and studied lncRNA APOC1P1-3 effects on apoptosis. Using Dual-Luciferase activity assay, we determined whether it specifically binds to miRNA-188-3P. We further explored its role in lung metastasis by injecting MDA-MB-231 and MDA-MB-231-APOC1P1-3-knock-down cells in female BALB/c nude mice. RESULTS: We found that lncRNA APOC1P1-3 suppressed early apoptosis of these cells (demonstrated by gain or loss of their function, respectively) and promoted anoikis resistance via reducing activated- Caspase 3, 8, 9 and PARP. Moreover, it specifically binds to the target miRNA-188-3p acting as a "sponge" to block the inhibition of Bcl-2 (an anti-apoptosis protein). CONCLUSIONS: Our study supports a theory that lncRNA APOC1P1-3 can promote development of breast cancer metastasis via anoikis resistance by specifically binding to miRNA-188-3p to block the inhibition of Bcl-2.
Entities:
Keywords:
Anoikis resistance; Breast cancer; LncRNA APOC1P1-3; MiRNA-188-3p; Tumor metastasis