METTL3-mediated m6A modification of PARP2 accelerates hepatocellular carcinoma progression.

Authors

Mengke Li, Yan Zhao, Yuan Li

Published in

Toxicology and applied pharmacology. Pages 118069. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

Hepatocellular carcinoma is a common primary liver cancer with high death rate worldwide. Poly ADP-ribose polymerase 2 (PARP2) has been reported to promote hepatocellular carcinoma cell growth. In this study, we aimed to explore the role of PARP2 in the progression of hepatocellular carcinoma and the underlying mechanisms at the transcriptional modification level. The protein expression of PARP2, methyltransferase-like 3 (METTL3), insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), and IGF2BP3 was determined by western blotting. MTT assay was utilized to measure cell viability. Apoptosis was evaluated by flow cytometry. Transwell invasion assay was conducted to evaluate cell invasion. MeRIP-qPCR, RIP-qPCR, and RNA stability analysis were performed to identify whether METTL3, IGF2BP2, and IGF2BP3 regulate the N6-methyladenosine (m6A) modification of PARP2. Results showed that PARP2 was highly expressed in hepatocellular carcinoma and related to its poor prognosis. Knockdown of PARP2 induced apoptosis and suppressed the viability and invasion in hepatocellular carcinoma cells. METTL3 expression was increased in hepatocellular carcinoma and positively associated with PARP2 expression. METTL3 regulated PARP2 expression by modulating its m6A modification. Moreover, PARP2 was recognized by the m6A "readers" IGF2BP2 and IGF2BP3. The effects of METTL3 knockdown on the malignant behaviors of hepatocellular carcinoma cells were reversed by PARP2 overexpression in vitro. Also, METTL3 depletion repressed tumor growth by regulating PARP2 expression in hepatocellular carcinoma xenograft mice in vivo. Our findings indicate that METTL3-mediated PARP2 m6A modification plays a vital tumor-promoter role in hepatocellular carcinoma progression.

PMID:
42833521
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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