Transcriptomic Analysis Reveals the MicroRNAs Responsible for Liver Regeneration Associated With Mortality in Alcohol-Associated Hepatitis.
Transcriptomic Analysis Reveals the MicroRNAs Responsible for Liver Regeneration Associated With Mortality in Alcohol-Associated Hepatitis.
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DOI：
10.1002/hep.31994
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Liangpunsakul S
中科院分区：
文献类型：
--
作者：
Yang Z;Zhang T;Kusumanchi P;Tang Q;Sun Z;Radaeva S;Peiffer B;Shah VH;Kamath P;Gores GJ;Sanyal A;Chalasani N;Jiang Y;Huda N;Ma J;Liangpunsakul S
我们进行了全面的血清转录组分析，以探讨 miRNA 在酒精性肝炎 (AH) 发病机制中的作用及其预后意义。对 15 名对照者、20 名无肝病的重度饮酒者和 65 名 AH 患者进行了血清 miRNA 分析，并与公开的 AH 患者肝脏 miRNA 分析进行了比较。在前 26 个 miRNA 中，AH 患者血清和肝脏中 miR-30b-5p、miR-20a-5p、miR-146a-5p 和 miR-26b-5p 的表达均显着降低。对这些 miRNA 潜在靶标的通路分析揭示了与 DNA 合成和细胞周期进展通路相关的基因，包括 RRM2、CCND1、CCND2、MYC 和 PMAIP1。我们发现接受肝移植的 AH 患者中 RRM2、CCND1 和 CCND2 的蛋白表达显着增加，但 MYC 和 PMAIP1 没有显着增加； miR-26b-5p和miR-30b-5p抑制RRM2和CCND2的3'-UTR荧光素酶活性，miR-20a-5p降低CCND1和CCND2的3'-UTR荧光素酶活性。在中位随访 346 天期间，21% 的 AH 患者死亡；这些患者的 BMI、MELD、血清 miR-30b-5p、miR-20a-5p、miR-146a-5p 和 miR-26b-5p 高于幸存者。 Cox回归分析显示BMI、MELD评分、miR-20a-5p、miR-146a-5p和miR-26b-5p可预测死亡率。 AH 患者试图通过下调特定 miRNA 和上调负责 DNA 合成和细胞周期进展的基因来应对肝细胞损伤。这些 miRNA 的较高表达表明肝再生能力下降，可预测 AH 患者的短期死亡率。
We conducted a comprehensive serum transcriptomic analysis to explore the roles of miRNAs in alcoholic hepatitis (AH) pathogenesis and their prognostic significance. Serum miRNA profiling was performed in 15 controls, 20 heavy drinkers without liver disease, and 65 patients with AH and compared to publicly available hepatic miRNA profiling in AH patients. Among the top 26 miRNAs, the expression of miR-30b-5p, miR-20a-5p, miR-146a-5p, and miR-26b-5p were significantly reduced in both serum and liver of AH patients. Pathway analysis of the potential targets of these miRNAs uncovered the genes related to DNA synthesis and cell cycle progression pathways, including RRM2, CCND1, CCND2, MYC, and PMAIP1. We found a significant increase in the protein expression of RRM2, CCND1, and CCND2, but not MYC and PMAIP1 in AH patients who underwent liver transplantation; miR-26b-5p and miR-30b-5p inhibited the 3’-UTR luciferase activity of RRM2 and CCND2, and miR-20a-5p reduced the 3’-UTR luciferase activity of CCND1 and CCND2. During a median follow-up of 346 days, 21% of AH patients died; these patients had higher BMI, MELD, serum miR-30b-5p, miR-20a-5p, miR-146a-5p, and miR-26b-5p than those who survived. Cox regression analysis showed BMI, MELD score, miR-20a-5p, miR-146a-5p, and miR-26b-5p predicted the mortality. Patients with AH attempt to deal with hepatocyte injury by down-regulating specific miRNAs and upregulating genes responsible for DNA synthesis and cell cycle progression. Higher expression of these miRNAs, suggestive of a diminished capacity in liver regeneration, predicts short-term mortality in AH patients.
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影响因子：
--
作者：
Li YL;Wang J;Zhang CY;Shen YQ;Wang HM;Ding L;Gu YC;Lou JT;Zhao XT;Ma ZL;Jin YX
通讯作者：
Jin YX
影响因子：
11.2
作者：
Kanlikilicer P;Rashed MH;Bayraktar R;Mitra R;Ivan C;Aslan B;Zhang X;Filant J;Silva AM;Rodriguez-Aguayo C;Bayraktar E;Pichler M;Ozpolat B;Calin GA;Sood AK;Lopez-Berestein G
通讯作者：
Lopez-Berestein G
影响因子：
29.4
作者：
Liangpunsakul S;Haber P;McCaughan GW
通讯作者：
McCaughan GW
影响因子：
24.5
作者：
Blaya, Delia;Coll, Mar;Sancho-Bru, Pau
通讯作者：
Sancho-Bru, Pau
DOI：
10.1016/j.clinre.2015.05.008
发表时间：
2015-09
影响因子：
2.7
作者：
Gao B;Shah VH
通讯作者：
Shah VH