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miR-98-5p as a novel biomarker suppress liver fibrosis by targeting TGFβ receptor 1

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Abstract

Background

Hepatic fibrosis is the repair reaction of excessive deposition and abnormal distribution of extracellular matrix after various liver injuries, especially chronic HBV infection, which is a key step in the development of various chronic liver diseases to cirrhosis. Recent studies have showed that microRNAs (miRNAs) can regulate a series of liver fibrosis-related gene express and play an important role in the development of liver fibrosis. But the miRNAs expression profiling and the differentially expressed miRNAs in patients with HBV-related liver fibrosis were little known. This study aims to have a record of a systemic screening for liver fibrosis-associated miRNAs in patients infected with HBV.

Methods

A IlluminaHiSeq sequencing of plasma miRNAs from the HBV-related liver fibrosis patients (S2/3, n = 8) based on Scheuer’s staging criteria and from healthy volunteers 42 (n = 7) was performed. Cluster analysis and target gene prediction were performed for the differentially expressed miRNAs. Gene ontology (GO) analysis and KEGG pathway enrichment analysis also were performed on the differentially expressed target miRNA genes.

Results

Compared with the healthy control group, 77 miRNAs were screened out from the liver fibrosis group, among which 51 miRNAs were up-regulated and 26 miRNAs were down-regulated. Eventually, miR-98-5p was identified as a candidate predictor of liver fibrosis progression. miR-98-5p is reduced in activated LX2 cells, and miR-98-5p overexpression inhibited the HSCs activation. Mechanically, MiR-98-5p prevents liver fibrosis by targeting TGFbR1 and blocking TGFb1/Smad3 signaling pathway. Furthermore, serum miR-98-5p levels were measured from a total of 70 recruited patients with chronic HBV infection and 29 healthy individuals as controls. Serum miR-98-5p level was significantly lower in patients with liver fibrosis than in healthy controls and HBV carriers.

Conclusions

The expression of miRNAs in patients with liver fibrosis is significantly different from that of healthy volunteers. Many signal pathways of hepatic fibrosis are regulated by miRNAs. The potential value of miR-98-5p is as diagnostic biomarkers and therapeutic targets for HBV-related liver fibrosis.

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Data availability

This is a resubmission of an earlier paper. The results/data/figures in this manuscript have not been published elsewhere, nor are they under consideration by another publisher.

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Funding

This work was supported by the Beijing Nova Program (No. Z201100006820051 to XY), National Science and Technology Major Project of China(2014ZX10005001 to HX, 2013ZX10002005 to JC), National Science and Technology Major Project of China(2017ZX10202202 to SY, 2018ZX10715-005 to SY), the Beijing municipal science and technology project of traditional Chinese medicine(JJ2014-25), the National Key Research and Development Program of China (No. 2017YFC0908104), the Seedling raising plan of Beijing Ditan Hospital, Capital Medical University (DTYM201616), Beijing Municipal Administration of Hospitals (No.ZYLX201402, No. DFL2015170) and Capital's Funds for Health Improvement and Research (CFH 2020–1-2171).

Author information

Author notes

  1. Yanhua Ma and Xiaoxue Yuan contributed equally to this work.

Authors and Affiliations

  1. Peking University Ditan Teaching Hospital, Peking University Health Science Center, Beijing, China

    Yanhua Ma, Yifan Xu, Jun Chen & Huichun Xing

  2. Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, 8 East Jingshun Street, Beijing, 100015, China

    Yanhua Ma, Yifan Xu & Huichun Xing

  3. Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China

    Xiaoxue Yuan, Ming Han, Kai Han, Pu Liang, Shunai Liu & Jun Chen

  4. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, 8 East Jingshun Street, Beijing, 100015, China

    Xiaoxue Yuan, Ming Han, Kai Han, Pu Liang, Shunai Liu & Jun Chen

  5. Department of Infectious Diseases, Binzhou Medical University Hospital, Binzhou, Shandong, China

    Yanhua Ma

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  1. Yanhua Ma
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Contributions

YM and XY performed the experiments and wrote the manuscript; XY, MH, KH and PL collected blood samples from the HBV-related liver fibrosis patients; YM, XY, MH and YX analyzed and interpreted the data; SL contributed to scientific discussion; JC and HX designed the experiments, provided useful advice on the manuscript, and modified the manuscript.

Corresponding authors

Correspondence to Jun Chen or Huichun Xing.

Ethics declarations

Conflict of interest

Yanhua Ma, Xiaoxue Yuan, Ming Han, Yifan Xu, Kai Han, Pu Liang, Shunai Liu, Jun Chen, Huichun Xing declare no competing interests.

Animal research (ethics)

No animal experiments were involved in this study.

Consent to participate (ethics)

There is no conflict of interest to disclose. This is noted in the manuscript.

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All authors agreed for publication in Hepatology International as an Article.

Plant reproducibility

clinical trials registration This study has passed the ethical review and obtained the approval of the ethical review (No. 2013–061-2).

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Ma, Y., Yuan, X., Han, M. et al. miR-98-5p as a novel biomarker suppress liver fibrosis by targeting TGFβ receptor 1. Hepatol Int 16, 614–626 (2022). https://doi.org/10.1007/s12072-021-10277-5

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  • DOI: https://doi.org/10.1007/s12072-021-10277-5

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