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METTL3 promotes proliferation and invasion and inhibits ferroptosis in hepatocellular carcinoma by mediating m6A methylation modification of NUPR1.

Created on 07 Aug 2026

Authors

Yushan Zhao, Zhiyu Nan, Haojie Feng, Dong Wang

Published in

Molecular and cellular biochemistry. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

N6-methyladenosine (m6A) methylation modification plays an essential role in cancer development. This study focused on the mechanism exploration of m6A methyltransferase 3 (METTL3) and its downstream target gene nuclear protein-1 (NUPR1) in hepatocellular carcinoma (HCC). Detection of mRNA and protein was completed using real-time quantitative polymerase chain reaction and Western blot. Cellular behaviors were evaluated by CCK-8, EdU, flow cytometry and transwell assay. Ferroptosis was analyzed via Fe2+ level and oxidative indicators. Methylated RNA immunoprecipitation (MeRIP) was performed for validating m6A modification. RIP and dual-luciferase reporter assay were used to confirm METTL3 and NUPR1 combination. Animal research was implemented for METTL3 and NUPR1 analysis in vivo. METTL3 was overexpressed in HCC. METTL3 silencing suppressed HCC cell proliferation and invasion, while enhancing apoptosis and partially inducing ferroptosis. METTL3 downregulation reduced NUPR1 level. METTL3 induced m6A modification of NUPR1 in an IGF2BP2-dependent manner. Tumor-inhibitory effects of METTL3 knockdown were counteracted by NUPR1 overexpression. METTL3 promoted HCC tumor growth and suppressed ferroptosis in vivo by regulating NUPR1. These findings suggested that METTL3 facilitated cell invasion and partially inhibited ferroptosis through catalyzing m6A methylation modification of NUPR1, validating the specific regulatory axis METTL3/NUPR1 in HCC progression.

PMID:
42566146
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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