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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

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Abstract

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.

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Acknowledgements

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Funding

This work was supported by the Zhongshan Major Science and Technology Development Project (Zhong Ke Fa No. 2016B1002).

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  1. Mengqiu Wei and Peng Li contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Zhongshan People’s Hospital, Zhongshan City, Guangdong, China

    Kai Guo

  2. Department of Medical Intensive Care Unit, Zhongshan People’s Hospital, Zhongshan City, Guangdong, China

    Mengqiu Wei

  3. Department of Geriatrics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai City, Guangdong, China

    Peng Li

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MW and KG planned and designed the experiments, analyzed the data, and wrote the manuscript. MW performed the experiments and data collection. PL is responsible for re-analyzing data and revision.

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Correspondence to Kai Guo.

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Wei, M., Li, P. & Guo, K. The impact of PSRC1 overexpression on gene and transcript expression profiling in the livers of ApoE−/− mice fed a high-fat diet. Mol Cell Biochem 465, 125–139 (2020). https://doi.org/10.1007/s11010-019-03673-x

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