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An integrated analysis of the circRNA–miRNA–mRNA network reveals novel insights into potential mechanisms of cell proliferation during liver regeneration

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posted on 28.09.2019 by Gaiping Wang, Xueqiang Guo, Liya Cheng, Peipei Chu, Meng Chen, Yanhui Chen, Cuifang Chang

Cell proliferation constitutes the fundamental process and driving force behind regrowth during liver regeneration (LR). However, it remains unclear how competing endogenous RNA (ceRNA) networks affect hepatocyte proliferation and liver regeneration. Therefore, this study was designed to explore an LR-specific ceRNA network, which regulates cell proliferation. Based on the microarray data of mRNAs, and high-throughput sequencing data of miRNAs and circRNAs from regenerating livers, this study initially applied known 1484 LR associated mRNAs to perform GO analysis, and then selected 169 LR associated mRNAs involved in cell proliferation and the cell cycle. Subsequently, 188 interactive miRNA–mRNA pairs and 5206 circRNA–miRNA pairs, respectively, were predicted using bioinformatics methods. Next, in view of the differential expressions of these ceRNAs during LR, 26 miRNA–mRNA pairs and 71 circRNA–miRNA pairs were applied to generate a circRNA–miRNA–mRNA regulatory network, and only 14 triple interactive groups were obtained based on the predicted inverse interactions among ceRNAs. Finally, circ_19698/miR-423-5p axis was demonstrated to promote cell proliferation by modulating the expression of MYC, CCNA2, and CCND1 in rat BRL-3A cells. This study suggests a potential regulatory mechanism of cell proliferation in regenerating livers, as well as a novel pathway for modulating ceRNA networks to promote liver regeneration.

Funding

This work was financially supported by the National Natural Science Foundation of China [31572270], Natural Science Foundation of Henan Province [162300410181 and 182300410335], Henan Scientific and Technological Research Project [182102310244], Key Scientific Research Projects of Henan Higher Education [18A180019], and Henan Normal University’s Crossing Research Project [20170008] with Xinxiang Giant Industry and Trade Co., Ltd.

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