Screening of key mRNAs and microRNAs in rat liver regeneration using the element accumulation method and their roles in hepatocyte proliferation

王浚 孔维东 张继红 张春博 王子慧 薛奇杰

doi:10.16098/j.issn.0529-1356.2026.01.014

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (1) : 92-99. DOI: 10.16098/j.issn.0529-1356.2026.01.014

Screening of key mRNAs and microRNAs in rat liver regeneration using the element accumulation method and their roles in hepatocyte proliferation

WANG Jun ^{1, 2}, KONG Wei-dong ^{1, 2}, ZHANG Ji-hong ³, ZHANG Chun-bo ^{1, 2}, WANG Zi-hui^{1, 2}, XUE Qi-jie ^{1, 2}, XU Cun-shuan^{1, 2}, GUO Jian-lin ^{1, 2*}, WANG Gai-ping^{1, 2*}

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Abstract

Objective To elucidate the association between changes in mRNA and microRNA(miRNA) expression and reveal the regulatory patterns in hepatocyte proliferation during rat liver regeneration. MethodsA two-thirds partial hepatectomy (PH) model was established in rats using the Higgins method. Liver right lobe samples were collected at 10 time points (0, 2, 6, 12, 24, 30, 36, 72, 120, and 168 hours) after PH. Except for 0 time point, there were 6 rats in each of the other 9 time points, with 6 rats in the control group. mRNA and miRNA signal values in the liver tissue at each time point were quantitatively detected using microarrays. The signal values of mRNA and miRNA on 0 hour post-PH (three replicates) served as controls. The ratio values of mRNA and miRNA at other time points were calculated by dividing their signal values by the corresponding controls. The element accumulation method was employed to screen biologically significant, differentially expressed, related, and key mRNAs and miRNAs during specific phases of liver regeneration, the hepatocyte G₀/G₁ transition phase (including 2 and 6 hours post-PH), the proliferation phase (including 2, 6, 12, 24, 30, and 36 hours post-PH), and the G₁/G₀ transition phase (including 72, 120, and 168 hours post-PH). Bioinformatics method were used to analyze the functions, interactions, and expression correlations of the identified key mRNAs and miRNAs. ResultsA total of 13 927 mRNAs and 1166 miRNAs were detected across 10 time points during rat liver regeneration using biochip technology. By applying the element accumulation method, 946 key mRNAs and two key miRNAs novel701_mature and rattus morvegicus(rno)-miR-196a-5p were identified. Bioinformatics analysis revealed that novel701_mature interacted with TNFRSF12A mRNA, and rno-miR-196a-5p interacted with mRNAs of aquaporin 4(AQP4), BTB damin and CNC domain and CNC homolog 1(BACH1), CD244, homeo box B8(HOXB8), neurexin 1(NRXN1), periplacin(PPL), and TSC complex subunit 1(TSC1). Furthermore, the expression levels of these two miRNAs were up-regulated during the G₀/G₁ transition and proliferation phases, but down-regulated during the G₁/G₀ transition in hepatocytes. Conversely, the expression levels of the eight key mRNAs that interacted with these two miRNAs were up-regulated across all three phases (G₀/G₁ transition, proliferation, and G₁/G₀ transition) of hepatocyte proliferation. ConclusionThe two key miRNAs show expression correlation with identified eight target mRNAs and regulat hepatocyte proliferation and liver regeneration processes.

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/ "> Liver regeneration / Hepatocyte proliferation / Element accumulation method / RNA high-throughput detection technology / Rat

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WANG Jun , KONG Wei-dong , ZHANG Ji-hong , ZHANG Chun-bo, WANG Zi-hui, XUE Qi-jie , XU Cun-shuan , GUO Jian-lin , WANG Gai-ping.

Screening of key mRNAs and microRNAs in rat liver regeneration using the element accumulation method and their roles in hepatocyte proliferation

[J]. Acta Anatomica Sinica. 2026, 57(1): 92-99 https://doi.org/10.16098/j.issn.0529-1356.2026.01.014

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