Evidence map›Paper›PMID 38395762›Full record

ArticleBMC gastroenterology2024

miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells.

Jin-Pei Liu, Shao-Hua Song, Pei-Mei Shi, Xiao-Yu Qin, Bai-Nan Zheng, Shu-Qing Liu, Chen-Hong Ding, Xin Zhang, Wei-Fen Xie, Yi-Hai Shi and 1 more

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Article in BMC gastroenterology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Jin-Pei Liu *Department of Gastroenterology, Gongli Hospital of Shanghai Pudong New Area, 219 Miaopu Road, 200135, Shanghai, China.
Shao-Hua Song *Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 200025, Shanghai, China.
Pei-Mei ShiDepartment of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, 200003, Shanghai, China.
Xiao-Yu QinDepartment of Gastroenterology, Gongli Hospital of Shanghai Pudong New Area, 219 Miaopu Road, 200135, Shanghai, China.
Bai-Nan ZhengDepartment of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, 200003, Shanghai, China.
Shu-Qing LiuDepartment of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, 200003, Shanghai, China.
Chen-Hong DingDepartment of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, 200003, Shanghai, China.
Xin ZhangDepartment of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, 200003, Shanghai, China.
Wei-Fen XieDepartment of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, 200003, Shanghai, China. weifenxie@medmail.com.cn.
Yi-Hai ShiDepartment of Gastroenterology, Gongli Hospital of Shanghai Pudong New Area, 219 Miaopu Road, 200135, Shanghai, China. syh01206@glhospital.com.
Wen-Ping XuDepartment of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, 200003, Shanghai, China. xwp198527@sina.com.
Shanghai Changzheng Hospital · CNSecond Military Medical University · CNRuijin Hospital · CN

Funding

National Natural Science Foundation of China 82000581National Natural Science Foundation of China 82030021National Natural Science Foundation of China 82270681the Foundation of Gongli Hospital 2022GPY-A06the Medical Discipline Construction Project of Pudong Health Committee of Shanghai PWYgf2021-08the Shanghai Pudong New Area Science and Technology Development Fund for the People's Livelihood Research Project PKJ2021-Y14the Shanghai Sailing Program 20YF1448900
6 · The paper itself

Abstract

backgroundThe activation of hepatic stellate cells (HSCs) has been emphasized as a leading event of the pathogenesis of liver cirrhosis, while the exact mechanism of its activation is largely unknown. Furthermore, the novel non-invasive predictors of prognosis in cirrhotic patients warrant more exploration. miR-541 has been identified as a tumor suppressor in hepatocellular carcinoma and a regulator of fibrotic disease, such as lung fibrosis and renal fibrosis. However, its role in liver cirrhosis has not been reported.

methodsReal-time PCR was used to detect miR-541 expression in the liver tissues and sera of liver cirrhosis patients and in the human LX-2. Gain- and loss-of-function assays were performed to evaluate the effects of miR-541 on the activation of LX-2. Bioinformatics analysis and a luciferase reporter assay were conducted to investigate the target gene of miR-541.

resultsmiR-541 was downregulated in the tissues and sera of patients with liver cirrhosis, which was exacerbated by deteriorating disease severity. Importantly, the lower expression of miR-541 was associated with more episodes of complications including ascites and hepatic encephalopathy, a shorter overall lifespan, and decompensation-free survival. Moreover, multivariate Cox's regression analysis verified lower serum miR-541 as an independent risk factor for liver-related death in cirrhotic patients (HR = 0.394; 95% CI: 0.164-0.947; P = 0.037). miR-541 was also decreased in LX-2 cells activated by TGF-β and the overexpression of miR-541 inhibited the proliferation, activation and hydroxyproline secretion of LX-2 cells. JAG2 is an important ligand of Notch signaling and was identified as a direct target gene of miR-541. The expression of JAG2 was upregulated in the liver tissues of cirrhotic patients and was inversely correlated with miR-541 levels. A rescue assay further confirmed that JAG2 was involved in the function of miR-541 when regulating LX-2 activation and Notch signaling.

conclusionsDysregulation of miR-541/JAG2 axis might be a as a new mechanism of liver fibrosis, and miR-541 could serve as a novel non-invasive biomarker and therapeutic targets for liver cirrhosis.

Indexed as

Hepatic Stellate CellsLiver CirrhosisMicroRNAsCell ProliferationHumansJagged-2 ProteinPrognosisJAG2 protein, humanJagged-2 ProteinMicroRNAsMIRN541 microRNA, humanJAG2Liver cirrhosismiR-541Notch signaling pathwayPrognosis

Identifiers

PMID38395762
PMCPMC10893617
OpenAlexW4392099156

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.