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http://purl.uniprot.org/citations/37534933http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

N6-methyladenosine (m6A), the most prevalent internal RNA modification in eukaryotic cells, is dynamically regulated in response to a wide range of physiological and pathological states. Nonetheless, the involvement of METTL14-induced m6A in liver fibrosis (LF) has yet to be established.

Methods

In vitro, HSC cell lines with knock-down and overexpression of METTL14 were constructed, and the effects of METTL14 gene on the phenotypic function of activated HSCs were observed. The proliferation rate was measured by CCK8 and EDU, the cell proliferation cycle was measured by flow detector, the migration rate was measured by Transwell, and the contractility of F-actin was observed after phalloidin staining. The downstream target gene NOVA2 of METTL14 was screened by combined sequencing of MeRIP-seq and RNA-seq, combined with signal analysis. Adeno-associated virus (AAV) was injected into the tail vein in vivo to knock down the expression of METTL14, so as to further observe the role of METTL14 in the progress of LF.

Results

our research showed that the methylase METTL14 content was decreased in hepatic tissue from patients with LF, leading to a lowered degree of m6A modification. Functionally, we discovered that knocking down m6A methyltransferase METTL14 led to increased HSC activation and a substantial worsening of LF. Mechanically, as shown in a multiomics study of HSCs, depleting METTL14 levels decreased m6A deposition onNOVA2 mRNA transcripts, which prompted the activation of YTHDF2 to detect and degrade the decrease of NOVA2 mRNA.

Conclusions

METTL14 functioned as a profibrotic gene by suppressing NOVA2 activity in a mechanism dependent on m6A-YTHDF2. Moreover, knocking down METTL14 exacerbated LF, while NOVA2 prevented its development and partly reversed the damage."xsd:string
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http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Feng T."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Li J."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Li W."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Liu R."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Peng L."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Song J."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Zhang W."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Yuan H."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Zhu C."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/author"Hou X."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/name"Hepatol Commun"xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/pages"e0199"xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/title"METTL14 reverses liver fibrosis by inhibiting NOVA2 through an m6A-YTHDF2-dependent mechanism."xsd:string
http://purl.uniprot.org/citations/37534933http://purl.uniprot.org/core/volume"7"xsd:string
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