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

doi:10.11904/j.issn.1002-3070.2020.04.006

摘要/Abstract

摘要： 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。

关键词: 长链非编码RNA, HCP5, 三阴性乳腺癌

Abstract: 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.

Key words: lncRNA, HCP5, Triple negative breast cancer

中图分类号:

R739.9

仝潇, 邢佳妮, 王丽虹. 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[J]. 实用肿瘤学杂志, 2020, 34(4): 321-327.

TONG Xiao, XING Jiani, WANG Lihong. Long-chain noncoding RNA HCP5 promotes triple-negative breast cancer by regulating apoptotic pathway[J]. Journal of Practical Oncology, 2020, 34(4): 321-327.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2020.04.006

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2020/V34/I4/321

参考文献

1 Jemal A,Siegel R,Ward E,et al.Cancer statistics[J].CA Cancer J Clin,2009,59(4):225-249.
2 Fernandes J,Acuna SM,Aoki JI,et al.Long non-coding RNAs in the regulation of gene expression[J].Noncoding RNA,2019,5(1):17.
3 Yang Y,Yang H,Xu M,et al.Long non-coding RNA(lncRNA)MAGI2-AS3 inhibits breast cancer cell growth by targeting the Fas/FasL signalling pathway[J].Hum Cell,2018,31(3):232-241.
4 Gradia DF,Mathias C,Coutinho R,et al.Long non-coding RNA TUG1 expression is associated with different subtypes in human breast cancer[J].Noncoding RNA,2017,3(4):26.
5 Liu Y,Helms C,Liao W,et al.A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci[J].PLoS Genet,2008,4(3):e1000041.
6 Lange CM,Bibert S,Dufour JF,et al.Comparative genetic analyses point to HCP5 as susceptibility locus for HCV-associated hepatocellular carcinoma[J].J Hepatol,2013,59(3):504-509.
7 Zhu TG,Xiao X,Wei Q,et al.Revealing potential long non-coding RNA biomarkers in lung adenocarcinoma using long non-coding RNA-mediated competitive endogenous RNA network[J].Braz J Med Biol Res,2017,50(9):e6297.
8 Liu N,Zhang R,Zhao X,et al.A potential diagnostic marker for ovarian cancer:involvement of the histone acetyltransferase,human males absent on the first[J].Oncol Lett,2013,6(2):393-400.
9 Li J,Gao C,Liu C,et al.Four lncRNAs associated with breast cancer prognosis identified by coexpression network analysis[J].J Cell Physiol,2019,234(8):14019-14030.
10 孙坤,王冲,沈成凤,等.2015年天津市恶性肿瘤流行情况分析[J].实用肿瘤学杂志,2020,34(2):114-119.
11 Schimmer AD.Inhibitor of apoptosis proteins:translating basic knowledge into clinical practice[J].Can Res,2004,64(20):7183-7190.
12 Nachmias B,Ashhab Y,Ben-Yehuda D.The inhibitor of apoptosis protein family(IAPs):an emerging therapeutic target in cancer[J].Semin Cancer Biol,2004,14(4):231-243.
13 Bertrand MJ,Milutinovic S,Dickson KM,et al.cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination[J].Mol Cell,2008,30(6):689-700.
14 Dai Z,Zhu WG,Morrison CD,et al.A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes[J].Hum Mol Genet,2003,12(7):791-801.

[1]	李静, 王玉霞, 陈杰. 长链非编码RNA HOTAIR在宫颈癌中的相关研究进展[J]. 实用肿瘤学杂志, 2020, 34(4): 368-371.
[2]	郭永东, 靳晶, 李利敏, 贺宇彤. 分化拮抗非蛋白质编码RNA(DANCR)在常见恶性肿瘤中的研究进展[J]. 实用肿瘤学杂志, 2020, 34(1): 69-73.
[3]	刘耿淳, 申良方. 血清长链非编码RNA MALAT1和AFAP1-AS1与鼻咽癌临床病理特征和预后的关系[J]. 实用肿瘤学杂志, 2019, 33(6): 513-518.
[4]	李思维 , 庞达. 长链非编码RNA(lncRNA)在癌症中的作用[J]. 实用肿瘤学杂志, 2019, 33(5): 471-475.
[5]	赵金璐, 李国东刘明. 长链非编码RNA CCAT1与消化系统恶性肿瘤关系的研究进展[J]. 实用肿瘤学杂志, 2019, 33(4): 367-370.
[6]	李嘉琪,栾瑾微,张,玉,李香兰. 763例三阴性乳腺癌临床病理特征及复发、转移影响因素分析[J]. 实用肿瘤学杂志, 2019, 33(3): 244-249.
[7]	刘乙澍,曲国蕃. 长链非编码RNA在骨肉瘤中的研究进展[J]. 实用肿瘤学杂志, 2019, 33(3): 266-270.
[8]	徐文品, 焦琨(综述), 张伟(审校). 长链非编码RNAs在口腔鳞癌中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(3): 258-262.
[9]	杨钊, 赵世光. 长链非编码RNA CASC2抑制肿瘤发生发展的研究概况[J]. 实用肿瘤学杂志, 2018, 32(2): 179-183.
[10]	张中民, 庞达. 长链非编码RNA调控癌症细胞信号通路的研究进展[J]. 实用肿瘤学杂志, 2018, 32(2): 184-188.
[11]	余嘉惠, 刘煊, 李琦, 陆烨, 岳小强. 长链非编码RNA在胃癌中的调控机制及中药对其作用的研究概况[J]. 实用肿瘤学杂志, 2018, 32(1): 47-52.
[12]	申美莹, 庞达. 长链非编码RNA在肿瘤微环境中的调控作用[J]. 实用肿瘤学杂志, 2018, 32(1): 73-76.
[13]	罗佳宁, 郝春成, 张建鑫, 卢江岳, 葛晓峰. 术后辅助放疗对三阴性乳腺癌患者预后的影响[J]. 实用肿瘤学杂志, 2017, 31(5): 411-416.
[14]	陈芊霖，庞达. 长链非编码RNA EPB41L4A-AS2对乳腺癌的预后研究[J]. 实用肿瘤学杂志, 2017, 31(3): 205-210.
[15]	汤大北, 金艳, 龚振琴, 初众, 曹仲茹, 张清媛. 三阴性乳腺癌中miRNA-124表达与E-钙黏蛋白及雄激素受体的关系[J]. 实用肿瘤学杂志, 2017, 31(2): 97-101.