The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone

PeerJ

article

Changlin Qian¹  Weiqing Qiu²  Jie Zhang²  Zhiyong Shen²  Hua Liu²  Yongjie Zhang¹ 

[1] The Second Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University;Department of General Surgery, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

关键词: Cholesterol gallstone;    Animal modeling;    Library construction;    Differential expression analysis;    Enrichment analysis;    Competing endogenous RNA;   

DOI  :  10.7717/peerj.10803

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundCholesterol gallstone (CG) is the most common gallstone disease, which is induced by biliary cholesterol supersaturation. The purpose of this study is to investigate the pathogenesis of CG.MethodsSixteen mice were equally and randomly divided into model group and normal control group. The model group was fed with lithogenic diets to induce CG, and then gallbladder bile lipid analysis was performed. After RNA-seq library was constructed, differentially expressed mRNAs (DE-mRNAs) and differentially expressed lncRNAs (DE-lncRNAs) between model group and normal control group were analyzed by DESeq2 package. Using the cluster Profiler package, enrichment analysis for the DE-mRNAs was carried out. Based on Cytoscape software, the protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network were built. Using quantitative real-time reverse transcription-PCR (qRT-PCR) analysis, the key RNAs were validated.ResultsThe mouse model of CG was suc cessfully established, and then 181 DE-mRNAs and 33 DE-lncRNAs between model and normal groups were obtained. Moreover, KDM4A was selected as a hub node in the PPI network, and lncRNA MEG3 was considered as a key lncRNA in the regulatory network. Additionally, the miR-107-5p/miR-149-3p/miR-346-3-MEG3 regulatory pairs and MEG3-PABPC4/CEP131/NUMB1 co-expression pairs existed in the regulatory network. The qRT-PCR analysis showed that KDM4A expression was increased, and the expressions of MEG3, PABPC4, CEP131, and NUMB1 were downregulated.ConclusionThese RNAs might be related to the pathogenesis of CG.

【 授权许可】

CC BY