miR-95-3p通过上调MAPK15调控三阴性乳腺癌的增殖及凋亡  

miR-95-3p promotes the proliferation and inhibits the apoptosis in triple-negative breast cancer by up-regulating MAPK15 expression

作　　者：张伟[1] 彭燕琪 费思佳 何建军[1] 张慧敏[1] 王彬 许静[2] ZHANG Wei;PENG Yanqi;FEI Sijia;HE Jianjun;ZHANG Huimin;WANG Bin;XU Jing(Department of Breast Surgery,The First Affiliated Hospital of Xi’an Jiaotong University,Xi'an 710061,China;Department of Geriatric Endocrinology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院乳腺外科,陕西西安710061 [2]西安交通大学第一附属医院老年内分泌科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2020年第6期896-900,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省自然科学基础研究计划[一般项目(面上)](No.2020JM-393);西安交通大学第一附属医院教改项目(No.JG20190312);西安交通大学第一附属医院院基金(No.2017QN-16);陕西省重点研发计划(一般项目-社会发展领域)(No.2018SF-156)。

摘　　要：目的探讨miR-95-3p在三阴性乳腺癌癌组织中的表达及与乳腺癌发生发展的关系。方法收集2010年5月1日至2012年12月31日西安交通大学第一附属医院收治的经病理证实的167例三阴性乳腺癌患者的病史资料,采用qRT-PCR检测三阴性乳腺癌组织和癌旁组织中的miR-95-3p的表达水平,分析其表达与TNM分期的关系;MTT和流式细胞仪检测细胞的增殖和凋亡情况;细胞免疫组化检测MAPK15在细胞中的表达情况。结果miR-95-3p在三阴性乳腺癌组织中的表达明显高于癌旁组织(67%vs.23%);生存分析表明,miR-95-3p表达是预后的危险因素(P<0.05);单因素方差分析显示,三阴性乳腺癌组织中miR-95-3p的表达与T、N、M明显相关。qRT-PCR显示,相较于正常乳腺细胞,miR-95-3p在三阴性乳腺癌细胞中高表达。上调miR-95-3p之后,乳腺癌细胞的增殖能力增强,凋亡减少;下调miR-95-3p之后乳腺癌细胞的增殖能力减弱,凋亡增多。然而在非三阴性乳腺癌细胞系中,调控miR-95-3p后,乳腺癌细胞增殖及凋亡水平的改变不明显。通过Targetscan预测了miR-95-3p的下游MAPK15,发现其主要在三阴性乳腺癌细胞系中高表达。在三阴性乳腺癌细胞中,调控miR-95-3p后,MAPK15的表达明显改变。在非三阴性乳腺癌中,调控miR-95-3p后,MAPK15表达水平改变不明显。结论miR-95-3p在乳腺癌中高表达,主要在三阴性乳腺癌中通过调控MAPK15参与乳腺癌患者的疾病进展。Objective To evaluate the expression profile and role of miR-95-3p in the triple-negative breast cancer(TNBC)tissues.Methods We recruited histologically diagnosed TNBC patients from May 1,2010 to December 31,2012 at our hospital.qRT-PCR was used to detect the expression profile of miR-95-3p and its relationships with T,N and M stages.MTT and flow cytometry were used for evaluating the proliferation and apoptosis,respectively.Cell immune-fluorescence was used to evaluate MAPK15 expression.Results miR-95-3p was expressed more highly in TNBC cancer tissues than in para-cancer tissues(67%vs.23%).Survival analysis indicated that miR-95-3p expression was correlated with the overall survival(P<0.05);further one-way ANOVA test suggested that miR-95-3p expression was associated with T,N and M stages.qRT-PCR showed the higher expression of miR-95-3p in TNBC cell line.Up-regulation of miR-95-3p led to the increased cell proliferation rate and decreased apoptosis rate in contrast to the down-regulation of miR-95-3p.However,miR-95-3p failed to significantly affect the apoptosis and proliferation rate in MCF-7.Then MAPK15,the predicted target for miR-95-3p by Targetscan,was mainly overexpressed in MDA-MB-231 rather than in MCF-7.The up-regulation of miR-95-3p resulted in the overexpression of MAPK15 in MDA-MB-231.In MCF-7,regulation of miR-95-3p did not significantly influence the expression of MAPK15 in MCF-7.Conclusion miR-95-3p was expressed highly in TNBC and promoted cancer progression through up-regulating MAPK15.

关 键 词：miR-95-3p 三阴性乳腺癌 预后 增殖 凋亡 

分 类 号：R735.1[医药卫生—肿瘤]