长链非编码RNA HCP5通过调控凋亡通路促进三阴性乳腺癌的研究

Long-chain noncoding RNA HCP5 promotes triple-negative breast cancer by regulating apoptotic pathway

目的探讨长链非编码RNA(lncRNA)HCP5在三阴性乳腺癌中的作用及其机制。方法通过qPCR分析HCP5在乳腺癌细胞系和正常乳腺细胞系中的mRNA含量,RNA Scope方法分析HCP5在乳腺组织和癌组织中的表达;通过CCK-8实验和细胞存活/死亡实验分析敲低HCP5对三阴性乳腺癌细胞增殖能力的影响;裸鼠体内实验分析敲低HCP5对三阴性乳腺癌细胞成瘤能力的影响;抗体芯片技术分析敲低HCP5影响凋亡通路中BIRC3和Caspase-3蛋白的表达。结果与正常乳腺细胞和其他类型乳腺癌细胞相比,HCP5在三阴性乳腺癌细胞系中表达上调(P<0.05),与正常乳腺组织和其他亚型乳腺癌组织相比,HCP5在三阴性乳腺癌组织中表达上调(P<0.05);与对照组相比,HCP5敲低组三阴性乳腺癌细胞增殖减少、凋亡增加,且原位移植瘤的生长受到抑制(P<0.01);敲低HCP5引起凋亡通路中凋亡抑制因子BIRC3表达量降低、Caspase-3表达增加,差异具有统计学意义(P<0.05),对MAPK信号通路蛋白的影响组间差异无统计学意义。结论lncRNA HCP5通过调控细胞凋亡途径促进三阴性乳腺癌的恶性进展。

Objective The objective of this study was to explore the role and mechanism of long non-coding RNA(lncRNA)HCP5 in triple-negative breast cancer.Methods The mRNA content of HCP5 in breast cancer cell lines and normal breast cell lines was analyzed by qPCR,and the RNA Scope method was used to analyze the expression of HCP5 in breast tissues and breast cancer tissues.The effect of knocking-down HCP5 on the proliferation of triple negative breast cancer cells was analyzed by CCK-8 and cell survival/death experiments.The effect of knockdown HCP5 on the proliferative ability of breast cancer cells was analyzed in nude mice.Antibody microarray technique was used to analyze the effect of knockdown HCP5 on the expression of BIRC3 and caspase-3 proteins in the apoptotic pathway.Results Compared with normal breast cells and other types of breast cancer cells,HCP5 was up-regulated in triple negative breast cancer cell lines(P<0.05).Compared with normal breast tissues and other subtypes of breast cancers,HCP5 in triple negative breast cancer tissues were up-regulated(P<0.05).Compared with the control group,triple-negative breast cancer cells in the HCP5 knockdown group were decreased proliferation,increased apoptosis of triple negative breast cancer cells,and inhibited the growth of orthotopic tumor in nude mice(P<0.01).Knockdown of HCP5 caused a decrease expression of apoptotic inhibitor BIRC3 and an increase expression of Caspase-3 in the apoptotic pathway,the difference was statistically significant(P<0.05).There was no difference in the effect on the MAPK signaling pathway protein between wild and HCP5 knockdown groups.Conclusion lncRNA HCP5 promotes the malignant progression of triple negative breast cancer through regulating the apoptotic pathway.