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

Background Cholesterol 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. Methods Sixteen mice were equally and randomly divided into model group and normal control group. T...

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Main Authors: Changlin Qian, Weiqing Qiu, Jie Zhang, Zhiyong Shen, Hua Liu, Yongjie Zhang
Format: Article
Language:English
Published: PeerJ Inc. 2021-02-01
Series:PeerJ
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Online Access:https://peerj.com/articles/10803.pdf
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author Changlin Qian
Weiqing Qiu
Jie Zhang
Zhiyong Shen
Hua Liu
Yongjie Zhang
author_facet Changlin Qian
Weiqing Qiu
Jie Zhang
Zhiyong Shen
Hua Liu
Yongjie Zhang
author_sort Changlin Qian
collection DOAJ
description Background Cholesterol 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. Methods Sixteen 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. Results The 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. Conclusion These RNAs might be related to the pathogenesis of CG.
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spelling doaj.art-c6263422738a4f6d97595f5bfc83c93a2023-12-03T11:03:34ZengPeerJ Inc.PeerJ2167-83592021-02-019e1080310.7717/peerj.10803The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstoneChanglin Qian0Weiqing Qiu1Jie Zhang2Zhiyong Shen3Hua Liu4Yongjie Zhang5The Second Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, ChinaDepartment of General Surgery, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of General Surgery, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of General Surgery, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of General Surgery, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaThe Second Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, ChinaBackground Cholesterol 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. Methods Sixteen 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. Results The 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. Conclusion These RNAs might be related to the pathogenesis of CG.https://peerj.com/articles/10803.pdfCholesterol gallstoneAnimal modelingLibrary constructionDifferential expression analysisEnrichment analysisCompeting endogenous RNA
spellingShingle Changlin Qian
Weiqing Qiu
Jie Zhang
Zhiyong Shen
Hua Liu
Yongjie Zhang
The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone
PeerJ
Cholesterol gallstone
Animal modeling
Library construction
Differential expression analysis
Enrichment analysis
Competing endogenous RNA
title The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone
title_full The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone
title_fullStr The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone
title_full_unstemmed The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone
title_short The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone
title_sort long non coding rna meg3 plays critical roles in the pathogenesis of cholesterol gallstone
topic Cholesterol gallstone
Animal modeling
Library construction
Differential expression analysis
Enrichment analysis
Competing endogenous RNA
url https://peerj.com/articles/10803.pdf
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