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lncRNA 表达揭示了在大鼠肝再生过程中肝细胞增殖的潜在调控作用。

lncRNA Expression Reveals the Potential Regulatory Roles in Hepatocyte Proliferation during Rat Liver Regeneration.

机构信息

College of Life Science, Henan Normal University, Xinxiang 453007, Henan Province, China.

State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering and Drug Development, Xinxiang 453007, Henan Province, China.

出版信息

Biomed Res Int. 2019 Nov 11;2019:8597953. doi: 10.1155/2019/8597953. eCollection 2019.

Abstract

Liver regeneration is a tissue growth process after loss or injury of liver tissue, which is a compensatory hyperplasia rather than true regeneration, mainly depending on hepatocyte proliferation. Currently, a large number of studies on hepatocyte proliferation have been conducted. However, studies on the regulation of long noncoding RNA (lncRNA) on hepatocyte proliferation are still limited. To identify specially expressed lncRNA during rat liver regeneration, high-throughput sequencing technology was performed, and a total of 2446 lncRNAs and 4091 mRNAs were identified as significantly differentially expressed. Gene ontology (GO) enrichment analysis was performed to analyze the role of differentially expressed mRNAs, and 695 mRNAs were identified to be related to cell proliferation. Then, an lncRNA-mRNA coexpression network based on the differentially expressed lncRNAs and proliferation-related genes was constructed to analyze the potential function of lncRNAs on hepatocyte proliferation, and ten lncRNAs, NONRATT003557.2, NONRATT005357.2, NONRATT003292.2, NONRATT001466.2, NONRATT003289.2, NONRATT001047.2, NONRATT005180.2, NONRATT004419.2, NONRATT005336.2, and NONRATT005335.2, were selected as key regulatory factors, which may play crucial roles in hepatocyte proliferation during rat liver regeneration. Finally, a protein-protein interaction (PPI) network was established to illuminate the interaction between proliferation-related genes, and ten hub genes (Aurkb, Cdk1, Cdc20, Bub1b, Mad2l1, Kif11, Prc1, Ccna2, Top2a, and Ccnb1) were screened with the MCC method in the PPI network, which may be important biomarkers involved in the hepatocyte proliferation during rat liver regeneration. These results may provide clues for a more comprehensive understanding of the molecular mechanism of hepatocyte proliferation during rat liver regeneration.

摘要

肝再生是肝脏组织丢失或损伤后的组织生长过程,是一种代偿性增生而不是真正的再生,主要依赖于肝细胞增殖。目前,已经对肝细胞增殖进行了大量研究。然而,关于长链非编码 RNA(lncRNA)对肝细胞增殖的调节作用的研究仍然有限。为了鉴定大鼠肝再生过程中特异性表达的 lncRNA,采用高通量测序技术,共鉴定出 2446 个 lncRNA 和 4091 个 mRNA 作为显著差异表达。进行基因本体论(GO)富集分析以分析差异表达 mRNAs 的作用,鉴定出 695 个与细胞增殖相关的 mRNAs。然后,构建基于差异表达 lncRNAs 和增殖相关基因的 lncRNA-mRNA 共表达网络,分析 lncRNAs 对肝细胞增殖的潜在功能,选择 10 个 lncRNA,NONRATT003557.2、NONRATT005357.2、NONRATT003292.2、NONRATT001466.2、NONRATT003289.2、NONRATT001047.2、NONRATT005180.2、NONRATT004419.2、NONRATT005336.2 和 NONRATT005335.2,作为关键调控因子,可能在大鼠肝再生过程中对肝细胞增殖起关键作用。最后,建立蛋白质-蛋白质相互作用(PPI)网络,阐明增殖相关基因之间的相互作用,利用 PPI 网络中的 MCC 方法筛选出 10 个枢纽基因(Aurkb、Cdk1、Cdc20、Bub1b、Mad2l1、Kif11、Prc1、Ccna2、Top2a 和 Ccnb1),它们可能是大鼠肝再生过程中参与肝细胞增殖的重要生物标志物。这些结果可能为更全面地了解大鼠肝再生过程中肝细胞增殖的分子机制提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/593a/6885160/8214697b0a92/BMRI2019-8597953.001.jpg

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