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The impact of PSRC1 overexpression on gene and transcript expression profiling in the livers of ApoE-/- mice fed a high-fat diet.
Molecular and Cellular Biochemistry ( IF 4.3 ) Pub Date : 2019-12-14 , DOI: 10.1007/s11010-019-03673-x
Mengqiu Wei 1 , Peng Li 2 , Kai Guo 3
Affiliation  

Our previous studies have confirmed that proline/serine-rich coiled-coil 1 (PSRC1) overexpression can regulate blood lipid levels and inhibit atherosclerosis (AS) development. In the current study, the gene and transcript expression profiles in the livers of ApoE-/- mice overexpressing PSRC1 were investigated. HiSeq X Ten RNA sequencing (RNA-seq) analysis was used to examine the differentially expressed genes (DEGs) and differentially expressed transcripts in the livers of PSRC1-overexpressing ApoE-/- and control mice. Then, Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these DEGs and on long noncoding RNA (lncRNA) predicted target genes. A total of 1892 significant DEGs were identified: 1431 were upregulated (e.g., Cyp2a4, Obp2a, and Sertad4), and 461 were downregulated (e.g., Moxd1, Egr1, and Elovl3). In addition, 8184 significant differentially expressed transcripts were identified, 4908 of which were upregulated and 3276 of which were downregulated. Furthermore, 1106 significant differentially expressed lncRNAs were detected, 713 of which were upregulated and 393 of which were downregulated. Quantitative reverse transcription PCR (qRT-PCR) verified changes in 10 randomly selected DEGs. GO analyses showed that the DEGs and predicted lncRNA target genes were mostly enriched for actin binding and lipid metabolism. KEGG biological pathway analyses showed that the DEGs in the livers of PSRC1-overexpressing ApoE-/- mice were enriched in the mitogen-activated protein kinase (MAPK) pathway. These findings reveal that PSRC1 may affect liver actin polymerization and cholesterol metabolism-related genes or pathways. These mRNAs and lncRNAs may represent new biomarkers and targets for the diagnosis and therapy of lipid metabolism disturbance and AS.

中文翻译:

PSRC1过表达对高脂饮食的ApoE-/-小鼠肝脏中基因和转录本表达谱的影响。

我们以前的研究已经证实,脯氨酸/富含丝氨酸的卷曲螺旋1(PSRC1)的过表达可以调节血脂水平并抑制动脉粥样硬化(AS)的发展。在当前的研究中,研究了过表达PSRC1的ApoE-/-小鼠肝脏中的基因和转录本表达谱。HiSeq X十个RNA测序(RNA-seq)分析用于检查过表达PSRC1的ApoE-/-和对照小鼠肝脏中的差异表达基因(DEG)和差异表达的转录本。然后,对这些DEG和长的非编码RNA(lncRNA)预测的靶标基因进行了基因本体论(GO)功能富集和《京都议定书》的基因与基因组百科全书(KEGG)途径富集分析。总共确定了1892个重要的DEG:1431个上调(例如Cyp2a4,Obp2a和Sertad4),和461被下调(例如Moxd1,Egr1和Elovl3)。另外,鉴定了8184个显着差异表达的转录本,其中4908个被上调,其中3276个被下调。此外,检测到1106个显着差异表达的lncRNA,其中上调了713个,下调了393个。定量逆转录PCR(qRT-PCR)验证了10个随机选择的DEG的变化。GO分析表明,DEG和预测的lncRNA靶基因在肌动蛋白结合和脂质代谢方面最丰富。KEGG生物学途径分析表明,过表达PSRC1的ApoE-/-小鼠肝脏中的DEG富含促分裂原激活的蛋白激酶(MAPK)途径。这些发现表明PSRC1可能会影响肝脏肌动蛋白的聚合以及与胆固醇代谢相关的基因或途径。这些mRNA和lncRNAs可能代表脂质代谢障碍和AS的诊断和治疗的新的生物标志物和靶标。
更新日期:2019-12-17
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