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

lncRNA APOC1P1-3 promoting anoikis-resistance of breast cancer cells.
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lncRNA APOC1P1-3促进乳腺癌细胞失巢凋亡抵抗

DOI:
10.1186/s12935-021-01916-w
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发表时间:
2021-04-26
影响因子:
5.8
通讯作者:
Zhou P
Zhou P
中科院分区:
医学2区
文献类型:
--
作者:
Lu Q;Wang L;Gao Y;Zhu P;Li L;Wang X;Jin Y;Zhi X;Yu J;Li X;Qin X;Zhou P

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背景失巢凋亡抵抗通过允许癌细胞在体循环中存活而在肿瘤转移中起关键作用。我们以前发现,长的非编码RNA APOC 1 P1 -3(lncRNA APOC 1 P1 -3)抑制乳腺癌细胞的凋亡。在这项研究中,我们探讨了它在anoikis resistance.MethodsWe诱导的两个乳腺癌细胞系(MCF-7和MDA-MB-231)的anoikis抵抗锚定非依赖性培养条件下,研究lncRNA APOC 1 P1 -3对细胞凋亡的影响。使用双荧光素酶活性测定,我们确定它是否特异性结合miRNA-188- 3 P。我们进一步探讨其在肺转移中的作用,通过注射MDA-MB-231和MDA-MB-231-APOC 1 -3-knockdown细胞在雌性BALB/c nude mice.ResultsWe发现lncRNA APOC 1 -3抑制这些细胞的早期凋亡(表现为获得或丧失其功能,分别),并通过减少活化的Caspase 3,8,9和PARP促进抗失巢凋亡。此外,它特异性地结合到目标miRNA-188- 3 p作为“海绵”,以阻止Bcl-2的抑制(一种抗凋亡蛋白).ConclusionsOur研究支持的理论,lncRNA APOC 1 -3可以促进乳腺癌转移的发展,通过失巢凋亡抵抗通过特异性结合到miRNA-188- 3 p,以阻止Bcl-2的抑制。
BackgroundAnoikis 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.MethodsWe 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.ResultsWe 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).ConclusionsOur 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.
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