Evidence mapPaperPMID 41239427Full record

ArticleCancer cell international2025

The VCPKMT-VCP-HDAC1 axis inhibits colorectal cancer by conferring sensitivity to ferroptosis.

Cijun Huang, Jinlong Lin, Shuidan Xu, Yongrui Lv, Jiewei Chen, Jinghua Cao, Dan Xie, Fengwei Wang

Abstract read
In one paragraph

Article in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Cijun Huang *State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Jinlong Lin *State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Shuidan XuState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Yongrui LvState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Jiewei ChenState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Jinghua CaoState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Dan XieState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. xiedan@sysucc.org.cn.
Fengwei WangState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. wangfengw@sysucc.org.cn.

Funding

National Key R&D Program of China 2021YFA1300201National Natural Science Foundation of China 82372620National Natural Science Foundation of China 82503597Postdoctoral Fellowship Program of CPSF GZB20250509
6 · The paper itself

Abstract

backgroundFerroptosis, a regulated form of cell death driven by lipid peroxidation and iron dysregulation, plays a critical role in tumor suppression. The expression of certain genes determine ferroptosis sensitivity and may serve as biomarkers to identify patients who could benefit from ferroptosis-promoting therapies. The role of Methyltransferase-like (METTL) family proteins in colorectal cancer (CRC) tumorigenesis has gained increasing attention, yet the functional relevance of METTL21D (also known as VCPKMT) remains largely unexplored.

methodsCCK8 assays, colony formation assays, and xenograft tumor experiments were used to investigate the role of VCPKMT in proliferation and ferroptosis sensitivity in CRC. RNA sequencing, IP-MS, and RT-qPCR were used to identify the relevant genes of VCPKMT. Co-IP and subcellular fractionation assays, western blotting and immunofluorescence (IF) staining were used to explore the underlying molecular mechanisms of actions of VCPKMT.

resultsHerein, we identified that VCPKMT is downregulated in CRC tissues and lower VCPKMT expression correlates with ferroptosis resistance and poorer prognosis. Mechanistically, VCPKMT-induced VCP methylation facilitates its nuclear translocation, a process that enhances VCP's interaction with HDAC1. This interaction promotes the degradation of HDAC1 via the ubiquitin-proteasome pathway, leading to reduced expression of FTH1, a key inhibitor of ferroptosis. Combined targeting of HDAC1 and ferroptosis synergistically suppressed the growth of tumors with low VCPKMT expression.

conclusionsOur findings reveal a novel role for VCPKMT as a regulator of ferroptosis sensitivity in CRC, highlighting the VCPKMT-VCP-HDAC1 axis as a potential therapeutic target for CRC treatment.

Indexed as

Colorectal cancerFerroptosisHDAC1VCPVCPKMT

Identifiers

PMID41239427
PMCPMC12619479

What Socratic holds

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