摘要
背景与目的:长链非编码RNA 909(LINC00909)是一个新发现的长度约为2 kb的长链非编码RNA(lncRNA),在胶质瘤和白血病中被报道发挥癌基因的作用。然而LINC00909在胰腺癌中的作用鲜有报道。本研究旨探讨LINC00909在胰腺癌中的表达及其对患者预后的影响,以及LINC00909与其调控网络对胰腺癌细胞生物学行为的影响。方法:通过Ualcan在线分析LINC00909在TCGA数据库中24种肿瘤组织中的表达情况。通过Linked Omics在线分析LINC00909在176例胰腺癌中的表达及预后情况。利用lncRNA-miRNA结合数据库(star Base)及3个miRNA-mRNA结合数据库(miRmap、miRanda和Target Scan),预测LINC00909的靶microRNA(miRNA)以及靶miRNA下游的mRNA,并构建LINC00909-miRNA-mRNA网络。用R语言“limma”包对癌旁和癌组织的miRNA进行表达差异对比分析。利用R语言“survival”包、“survminer”包及“ggstatsplot”包,对所得到的基因进行生存分析及相关性分析。在胰腺癌PANC-1细胞上,用敲减实验(转染LINC00909 siRNA)分析LINC00909对PANC-1细胞增殖、迁移及侵袭的影响;用回复实验(同时转染LINC00909 siRNA与靶miRNA抑制剂)及验证LINC00909与靶miRNA之间的靶向关系。用双荧光素酶报告基因实验验证靶miRNA与LINC00909以及下游mRNA之间的互作关系。结果:Ualcan分析表明LINC00909在胰腺癌组织中低表达。Linked Omics分析表明LINC00909低表达患者的预后差(P<0.05)。通过star Base数据库获得28个与LINC00909结合的miRNA,进一步通过对TCGA胰腺癌miRNA表达数据分析发现,只有miR-194-5p在胰腺癌中表达明显上调。通过miRmap、miRanda和Target Scan数据库获得114个与miR-194-5p结合的潜在mRNA。进一步对114个mRNA进行表达相关性分析及生存分析,获得4个mRNA(DACH1、SOCS2、STX16及SNAP91),最终获得LINC00909-miR-194-5p-DACH1/SOCS2/STX16/SNAP91的ceRNA网络。敲减实验显示,LINC00909低表达组PANC-1细胞的增殖活力增加、划痕愈合率、迁�
Background and Aims:Long non-codingRNA 909(LINC00909)is a newly discovered long noncodingRNA(lncRNA)with a length of approximately 2 kb,which has been reported to function as an oncogene in gliomas and leukemias.However,the role of LINC00909 in pancreatic cancer has rarely been reported.This study was designated to investigate the expression of LINC00909 in pancreatic cancer and its influence on prognosis of the patients,as well as the impacts of LINC00909 and its regulatory network on the biological behaviors in pancreatic cancer cells.Methods:The expressions of LINC00909 in 24 different types of cancers in TCGA datasets were analyzed through UALCAN.Linked Omics was used to analyze the expressions of LINC00909 and prognosis in 176 pancreatic cancer patients were analyzed through Linked Omics database.By using the lncRNA-miRNA binding database(star Base)and three miRNA-mRNA binding databases(miRmap,miRanda,and Target Scan),the potential target microRNAs(miRNAs)of LINC00909 and the mRNAs downstream to these miRNAs were predicted,and the LINC00909-miRNA-mRNA network was constructed.The differentially expressed miRNAs between pancreatic cancer and adjacent non-tumorous pancreatic tissues were identified by the"limma"package of R language.The survival analysis and correlation analysis were conducted by using"survival","survminer",and"ggstatsplot"packages in R language.In pancreatic cancer PANC-1 cells,the influences of LINC00909 on cell proliferation,and migration/invasion abilities were investigated by a knockdown experiment(LINC00909 siRNA transfection),and the targeted relationship between LINC00909 and the potential miRNAs were verified by a rescue experiment(simultaneous transfection of LINC00909 siRNA and miRNA inhibitor).The interactions of the target miRNAs and with LINC00909 and their downstream mRNAs were verified by dual luciferase reporter assay.Results:UALCAN analysis revealed that LINC00909 was lowly expressed in pancreatic cancer tissues.Low expression of LINC00909 predicted poor prognosis based on dat
作者
邓家琦
钱保林
张丽云
李明星
DENG Jiaqi;QIAN Baolin;ZHANG Liyun;LI Mingxing(Department of Ultrasound Medicine,the Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan 646000,China;Department of Hepatobiliary Surgery,the Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan 646000,China;Health Management Department,the Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan 646000,China)
出处
《中国普通外科杂志》
CAS
CSCD
北大核心
2022年第3期340-350,共11页
China Journal of General Surgery
基金
西南医科大学校级基金资助项目(2018-ZRQN-077)。
关键词
胰腺肿瘤
RNA
长链非编码
微RNAS
细胞增殖
肿瘤浸润
Pancreatic Neoplasms
RNA
Long Noncoding
Micro RNAs
Cell Proliferation
Neoplasm Invasiveness
