Kong Lei, Wu Qinghua, Zhao Liangchao, Ye Jinhua, Li Nengping, Yang Huali
Department of General Surgery, Ruijin Hospital North, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Department of Ultrasound, Shanghai Fourth People's Hospital, Shanghai, China.
J Cell Biochem. 2019 Dec;120(12):19377-19387. doi: 10.1002/jcb.28953. Epub 2019 Sep 9.
The present study aimed to investigate the long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in the progression of gallbladder cancer and explore the potential physiopathologic mechanisms of gallbladder cancer in terms of competing endogenous RNAs (ceRNAs). The original lncRNA and mRNA expression profile data (nine gallbladder cancer tissues samples and nine normal gallbladder samples) in GSE76633 was downloaded from the Gene Expression Omnibus database. Differentially expressed mRNAs and lncRNAs between gallbladder cancer tissue and normal control were selected and the pathways in which they are involved were analyzed using bioinformatics analyses. MicroRNAs (miRNAs) were also predicted based on the differentially expressed mRNAs. Finally, the co-expression relation between lncRNA and mRNA was analyzed and the ceRNA network was constructed by combining the lncRNA-miRNA, miRNA-mRNA, and lncRNA-mRNA pairs. Overall, 373 significantly differentially expressed mRNAs and 47 lncRNAs were identified between cancer and normal tissue samples. The upregulated genes were significantly enriched in the extracellular matrix (ECM)-receptor interaction pathway, while the downregulated genes were involved in the complement and coagulation cascades. Altogether, 128 co-expression relations between lncRNA and mRNA were obtained. In addition, 196 miRNA-mRNA regulatory relations and 145 miRNA-lncRNA relation pairs were predicted. Finally, the lncRNA-miRNA-gene ceRNA network was constructed by combining the three types of relation pairs, such as XLOC_011309-miR-548c-3p-SPOCK1 and XLOC_012588-miR-765-CEACAM6. mRNAs and lncRNAs may be involved in gallbladder cancer progression via ECM-receptor interaction pathways and the complement and coagulation cascades. Moreover, ceRNAs such as XLOC_011309-miR-548c-3p-SPOCK1 and XLOC_012588-miR-765-CEACAM6 can also be implicated in the pathogenesis of gallbladder cancer.
本研究旨在探究参与胆囊癌进展的长链非编码RNA(lncRNA)和信使RNA(mRNA),并从竞争性内源RNA(ceRNA)角度探索胆囊癌潜在的生理病理机制。从基因表达综合数据库下载了GSE76633中的原始lncRNA和mRNA表达谱数据(9个胆囊癌组织样本和9个正常胆囊样本)。选取胆囊癌组织与正常对照之间差异表达的mRNA和lncRNA,并使用生物信息学分析方法分析它们所涉及的通路。还基于差异表达的mRNA预测了微小RNA(miRNA)。最后,分析lncRNA与mRNA之间的共表达关系,并通过整合lncRNA-miRNA、miRNA-mRNA和lncRNA-mRNA对构建ceRNA网络。总体而言,在癌组织与正常组织样本之间鉴定出373个显著差异表达的mRNA和47个lncRNA。上调基因显著富集于细胞外基质(ECM)-受体相互作用通路,而下调基因则参与补体和凝血级联反应。共获得128个lncRNA与mRNA之间的共表达关系。此外,预测出196个miRNA-mRNA调控关系和145个miRNA-lncRNA关系对。最后,通过整合XLOC_011309-miR-548c-3p-SPOCK1和XLOC_012588-miR-765-CEACAM6等三种类型的关系对构建了lncRNA-miRNA-基因ceRNA网络。mRNA和lncRNA可能通过ECM-受体相互作用通路以及补体和凝血级联反应参与胆囊癌进展。此外,诸如XLOC_011309-miR-548c-3p-SPOCK1和XLOC_012588-miR-765-CEACAM6等ceRNA也可能与胆囊癌的发病机制有关。