长链非编码RNA PVT1诱导直肠癌细胞增殖、抑制凋亡并通过上调Atg5诱导其自噬  

Long non-coding RNA PVT1 induces proliferation,inhibits apoptosis,and induces autophagy by up-regulating Atg5 in rectal cancer cells

作　　者：朱渊东 刘海源[1] 雷鑫明 彭雪强 Yuan-Dong Zhu;Hai-Yuan Liu;Xin-Ming Lei;Xue-Qiang Peng(Department of Anorectal Surgery,Yiwu Central Hospital,Jinhua 322000,Zhejiang Province,China;Department of Gastroenterology,Quzhou People’s Hospital,Quzhou 324000,Zhejiang Province,China;China Medical University,Shenyang 110000,Liaoning Province,China)

机构地区：[1]义乌市中心医院肛肠外科,浙江省金华市322000 [2]衢州市人民医院消化内科,浙江省衢州市324000 [3]中国医科大学,辽宁省沈阳市110000

出　　处：《世界华人消化杂志》2023年第8期307-315,共9页World Chinese Journal of Digestology

基　　金：义乌市科研计划项目,No.20-3-165.

摘　　要：背景lncRNA PVT1基因作为lncRNAs的一种,已经被证实在多种肿瘤中发挥促癌作用,但对于该基因在直肠癌中的生物学行为报道较少,因此,本研究在结合国内外研究的基础上,探讨lncRNA PVT1在直肠癌中表达以及与预后的关系,以及对直肠癌自噬的调控机制和增殖凋亡的影响,为直肠癌的靶向治疗提供可靠的靶点.目的探究lncRNA PVT1在直肠癌组织中的表达及对直肠癌细胞自噬和增值侵袭的影响.方法通过TCGA数据库获得92例直肠癌,318例健康样本的lncRNA PVT1表达水平,并且通过定量实时PCR检测直肠癌细胞SW837,HR8348,SW1463和FHC中lncRNA PVT1表达水平.通过R语言包(survival,survminer)分析TCGA数据库分析lncRNA PVT1表达高低与直肠癌预后的关系.过表达SW837,HR8348中的lncRNA PVT1.利用transwell,CCK-8试剂盒、流式细胞实验分析其侵袭,增值能力及凋亡的改变.然后Western blot实验分析LC3-II/LC3-I的表达,免疫荧光实验分析LC3荧光斑点的改变,透射电镜分析形态学判断自噬小体的改变.之后共转染si-Atg5分析直肠癌细胞自噬水平的变化.结果LncRNA PVT1在直肠癌组织和细胞中表达都显著增加.并且lncRNA PVT1的表达直肠癌预后相关,过表达lncRNA PVT1后激活直肠癌自噬和诱导肿瘤细胞增殖,侵袭并且抑制其凋亡(P<0.05).结论LncRNA PVT1在直肠癌组织和细胞中均高表达,且与其预后显著相关,过表达lncRNA PVT1诱导直肠癌细胞增殖,侵袭并抑制其凋亡.LncRNA PVT1通过调控Atg5的表达参与直肠癌自噬水平的调控,其可能参与直肠癌的发生发展.BACKGROUND As a long noncoding RNA(lncRNA),PVT1 has been proved to play a role in promoting cancer in many tumors,but there are few reports on its impact on the biological behavior of rectal cancer.Therefore,this study investigated the expression of lncRNA PVT1 in rectal cancer and its relationship with prognosis,as well as its effect on rectal cancer cell autophagy,proliferation,and apoptosis,so as to provide a reliable target for treatment of rectal cancer.AIM To investigate the expression of lncRNA PVT1 in rectal cancer and its effects on autophagy and proliferation of rectal cancer cells.METHODS The expression data of lncRNA PVT1 in 92 rectal cancer samples and 318 healthy control samples were obtained from the GEPIA database,and the expression levels of lncRNA PVT1 in rectal cancer cell lines SW837,HR8348,SW1463,and FHC were detected by quantitative real-time PCR.The relationship between the expression level of lncRNA PVT1 and the prognosis of rectal cancer was analyzed using the R packages(survival and survminer)based on the TCGA database.Overexpression of lncRNA PVT1 was then induced in SW837 and HR8348 cells.Transwell assay,CCK-8 assay,and flow cytometry were used to analyze the changes of cell invasion,proliferation,and apoptosis.Western blot analysis was performed to detect the expression of LC3-II/LC3-I,immunofluorescence was used to analyze the change of LC3 expression,and transmission electron microscopy was used to determine the change of autophagosomes.After co-transfection with si-Atg5,the changes of rectal cancer cell autophagy were analyzed.RESULTS The expression of lncRNA PVT1 in rectal cancer tissues and cells increased significantly.The expression of lncRNA PVT1 was related to the prognosis of rectal cancer.Overexpression of lncRNA PVT1 activated autophagy of rectal cancer cells and induced tumor cell proliferation,invasion,and apoptosis inhibition(P<0.05).CONCLUSION LncRNA PVT1 is highly expressed in rectal cancer tissues and cells,and is significantly related to the prognosis of rectal canc

关 键 词：直肠癌 LncRNA PVT1 增殖和凋亡 自噬 自噬相关5同源物 

分 类 号：R735.37[医药卫生—肿瘤]