贵州医科大学学报

2019, v.44;No.227(08) 875-880

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长链非编码RNA ITGβ2-AS1对胰腺癌MAPK信号通路的作用及机制
Bioinformatic Analysis of the Role of Long Non-coding RNA ITGβ2-AS1 in MAPK Signaling Pathway of Pancreatic Cancerand Its Mechanism

陈世裕;喻超;潘耀振;陈玲;李琳;杨哲豪;吕彦霖;邓路;孙诚谊;
CHEN Shiyu;YU Chao;PAN Yaozhen;CHEN Ling;LI Lin;YANG Zhehao;LV Yanlin;DENG Lu;SUN Chengyi;Guizhou Medical University;Department of Hepatobiliary Surgery, the Affiliated Hospital of Guizhou Medical University;Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University;Guizhou Institute of Hepatobiliary,Pancreatic and Spleen Diseases;

摘要(Abstract):

目的:探讨长链非编码RNA整合素β2(ITGβ2)-AS1在胰腺癌(PC)丝裂原活化蛋白激酶(MAPK)信号通路中的作用及机制。方法:选择癌症基因组图谱(TCGA)中胰腺导管腺癌数据库PAAD的mRNA表达谱类型,根据TCGA数据库分析结果,选取与ITGβ2-AS1相关的基因中相关系数较大(Person系数>0.6)的基因进行GO富集分析,筛选出与ITGβ2-AS1的表达显著相关的基因及信号通路;采用实时荧光定量聚合酶链反应(qRT-PCR)及Western blot验证人PC细胞株PANC-1中相关mRNA及蛋白的表达。结果:GO分析显示,ITGβ2-AS1与PC的增殖及相关肿瘤信号通路转导密切相关;qRT-PCR及Western blot结果显示,与正常PANC-1细胞比较,干扰ITGβ2-AS1后,PANC-1细胞中BCL2、MMP9、MYC及磷酸化的ERK1/2的mRNA及蛋白表达水平下降(P<0.05)。结论:ITGβ2-AS1可能通过正向调控MAPK信号通路上靶基因的表达,促进PC细胞的增殖、侵袭及迁移。
Objective: To investigate the role long-chain non-coding RNA ITGβ2-AS1 in regulating mitogen-activated protein kinase(MAPK) signaling pathway in pancreatic adenocarcinoma(PAAD) and its mechanism.Methods:The mRNA expression profile of PAAD was selected from the Cancer Genome Atlas(TCGA) database. Genes with a correlation coefficient(Person coefficient>0.6) with ITGβ2-AS1 were selected for GO function annotation and KEGG pathway analysis. qPCR and Western blot were used to verifythe expression levels of candidate genes in human pancreatic cancer cell line PANC-1.Results:GO enrichment analysis showed that ITGβ2-AS1 was closely associated with pancreatic cancer cell proliferation. KEGGanalysis revealed that ITGβ2-AS1 was associated with signaling pathways which regulate cellular proliferation.qRT-PCR and Western blot results showed that ITGβ2-AS1 interference downregulated the mRNA and protein levels of BCL2, MMP9, MYC and phosphorylated ERK1/2 when compared with control(P<0.05).Conclusion:ITGβ2-AS1 may promote the proliferation, invasion and migration of pancreatic cancer cellsby positively regulating the expression of genes in the MAPK signaling pathway.

关键词(KeyWords): 长链非编码RNA;整合素β2;胰腺癌;丝裂原活化蛋白激酶;癌症基因组图谱;基因本体论;癌症基因组图谱
long non-coding RNA;ITGβ2;pancreatic cancer;mitogen-activated protein kinase;cancer genome map;gene ontology

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基金项目(Foundation): 国家自然科学基金(81860505,81860506);; 贵州省科学技术厅—贵州医科大学附属医院联合基金[黔科合LH字(2016)7229];; 贵州省肝胆外科临床医学研究中心[黔科合平台人才(2017)5404];; 贵州省高层次创新人才培养计划“十”层次人才,黔科合平台人才[(2016)5647];; 贵州省科学技术厅—贵阳医学院院士工作站肝胆外科分站[黔科合院士站(2015)4013];; 贵州省孙诚谊“肝胆胰脾疾病诊治”导师工作室,黔教研合[GZS(2016)09];; 贵州省第四批人才基地(贵州省外科人才培养基地)—[黔省专合字(2012)94];; 贵州省科技支撑计划项目[黔科合SY字(2015)3047]

作者(Author): 陈世裕;喻超;潘耀振;陈玲;李琳;杨哲豪;吕彦霖;邓路;孙诚谊;
CHEN Shiyu;YU Chao;PAN Yaozhen;CHEN Ling;LI Lin;YANG Zhehao;LV Yanlin;DENG Lu;SUN Chengyi;Guizhou Medical University;Department of Hepatobiliary Surgery, the Affiliated Hospital of Guizhou Medical University;Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University;Guizhou Institute of Hepatobiliary,Pancreatic and Spleen Diseases;

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DOI: 10.19367/j.cnki.1000-2707.2019.08.002

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