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The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone
PeerJ ( IF 2.7 ) Pub Date : 2021-02-23 , DOI: 10.7717/peerj.10803
Changlin Qian 1, 2 , Weiqing Qiu 2 , Jie Zhang 2 , Zhiyong Shen 2 , Hua Liu 2 , Yongjie Zhang 1
Affiliation  

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.

中文翻译:

长链非编码 RNA MEG3 在胆固醇结石的发病机制中起关键作用

背景胆固醇胆结石(CG)是最常见的胆结石疾病,由胆汁胆固醇过饱和引起。本研究的目的是探讨 CG 的发病机制。方法 16只小鼠均等随机分为模型组和正常对照组。模型组给予致石饲料诱导CG,然后进行胆囊胆汁脂质分析。构建RNA-seq文库后,通过DESeq2包分析模型组和正常对照组之间的差异表达mRNAs(DE-mRNAs)和差异表达lncRNAs(DE-lncRNAs)。使用 cluster Profiler 软件包,对 DE-mRNA 进行了富集分析。基于Cytoscape软件,构建了蛋白质-蛋白质相互作用(PPI)网络和竞争性内源RNA(ceRNA)网络。使用定量实时逆转录-PCR (qRT-PCR) 分析,验证了关键 RNA。结果CG小鼠模型成功建立,模型组与正常组之间共获得181个DE-mRNA和33个DE-lncRNA。此外,KDM4A被选为PPI网络中的枢纽节点,lncRNA MEG3被认为是调控网络中的关键lncRNA。此外,调控网络中存在 miR-107-5p/miR-149-3p/miR-346-3-MEG3 调控对和 MEG3-PABPC4/CEP131/NUMB1 共表达对。qRT-PCR分析显示KDM4A表达上调,MEG3、PABPC4、CEP131和NUMB1表达下调。结论 这些RNA可能与CG的发病机制有关。结果CG小鼠模型成功建立,模型组与正常组之间共获得181个DE-mRNA和33个DE-lncRNA。此外,KDM4A被选为PPI网络中的枢纽节点,lncRNA MEG3被认为是调控网络中的关键lncRNA。此外,调控网络中存在 miR-107-5p/miR-149-3p/miR-346-3-MEG3 调控对和 MEG3-PABPC4/CEP131/NUMB1 共表达对。qRT-PCR分析显示KDM4A表达上调,MEG3、PABPC4、CEP131和NUMB1表达下调。结论 这些RNA可能与CG的发病机制有关。结果CG小鼠模型成功建立,模型组与正常组之间共获得181个DE-mRNA和33个DE-lncRNA。此外,KDM4A被选为PPI网络中的枢纽节点,lncRNA MEG3被认为是调控网络中的关键lncRNA。此外,调控网络中存在 miR-107-5p/miR-149-3p/miR-346-3-MEG3 调控对和 MEG3-PABPC4/CEP131/NUMB1 共表达对。qRT-PCR分析显示KDM4A表达上调,MEG3、PABPC4、CEP131和NUMB1表达下调。结论 这些RNA可能与CG的发病机制有关。lncRNA MEG3被认为是调控网络中的关键lncRNA。此外,调控网络中存在 miR-107-5p/miR-149-3p/miR-346-3-MEG3 调控对和 MEG3-PABPC4/CEP131/NUMB1 共表达对。qRT-PCR分析显示KDM4A表达上调,MEG3、PABPC4、CEP131和NUMB1表达下调。结论 这些RNA可能与CG的发病机制有关。lncRNA MEG3被认为是调控网络中的关键lncRNA。此外,调控网络中存在 miR-107-5p/miR-149-3p/miR-346-3-MEG3 调控对和 MEG3-PABPC4/CEP131/NUMB1 共表达对。qRT-PCR分析显示KDM4A表达上调,MEG3、PABPC4、CEP131和NUMB1表达下调。结论 这些RNA可能与CG的发病机制有关。
更新日期:2021-02-23
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