lncRNA APOC1P1-3 promoting anoikis-resistance of breast cancer cells

• Main Authors: Qi Lu, Li Wang, Yabiao Gao, Ping Zhu, Luying Li, Xue Wang, Youping Jin, Xiuling Zhi, Jerry Yu, Xin Li, Xingjun Qin, Ping Zhou
• Format: Article
• Language: English
• Published: BMC 2021-04-01
• Series: Cancer Cell International
• Subjects: Breast cancer; LncRNA APOC1P1-3; Anoikis resistance; MiRNA-188-3p; Tumor metastasis
• Online Access: https://doi.org/10.1186/s12935-021-01916-w

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.