Evidence map›Paper›PMID 38438251›Full record

ArticleCancer science2024

SMYD4 monomethylates PRMT5 and forms a positive feedback loop to promote hepatocellular carcinoma progression.

Zhenyu Zhou, Zheng Chen, Qianlei Zhou, Shiyu Meng, Juanyi Shi, Sintim Mui, Hai Jiang, Jianhong Lin, Gui He, Wenbin Li and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 9 citations in OpenAlex.

  1. Identification of Epigenetic Regulator-Associated Genes in Keloid Disease Through Integrated Bulk and Single-Cell Transcriptomics With RT-qPCR Validation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  8. Genetic Alterations ofInternational journal of molecular sciences · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Zhenyu ZhouDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Zheng ChenDepartment of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China.
Qianlei ZhouGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Shiyu MengGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Juanyi ShiDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Sintim MuiDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Hai JiangDepartment of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.ORCID https://orcid.org/0000-0002-7148-4204
Jianhong LinDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Gui HeCellular & Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Wenbin LiGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Jianlong ZhangDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Jie WangDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Chuanchao HeDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Yongcong YanDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Zhiyu XiaoDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.ORCID https://orcid.org/0000-0002-2964-1552
Sun Yat-sen University · CNNanchang University · CN

Funding

Guangdong Provincial Department of Science and Technology 2020B1212060018Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University KLB09001Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [2013] 163National Natural Science Foundation of China 81902413National Natural Science Foundation of China 81960442National Natural Science Foundation of China 81971463National Natural Science Foundation of China 82073045National Natural Science Foundation of China 82103090Science and Technology Program of Guangdong Province 2022A1515012391Science and Technology Program of Guangdong Province, China 2018A030313809Science and Technology Program of Guangdong Province, China 2020A1515010232Science and Technology Program of Guangdong Province, China 2021A1515010109Science and Technology Program of Guangzhou 202201020311The fundamental Research Funds for the Central Universities, Sun Yat-sen University 2021gntd35
6 · The paper itself

Abstract

Both lysine and arginine methyltransferases are thought to be promising therapeutic targets for malignant tumors, yet how these methyltransferases function in malignant tumors, especially hepatocellular carcinoma (HCC), has not been fully elucidated. Here, we reported that SMYD4, a lysine methyltransferase, acts as an oncogene in HCC. SMYD4 was highly upregulated in HCC and promoted HCC cell proliferation and metastasis. Mechanistically, PRMT5, a well-known arginine methyltransferase, was identified as a SMYD4-binding protein. SMYD4 monomethylated PRMT5 and enhanced the interaction between PRMT5 and MEP50, thereby promoting the symmetrical dimethylation of H3R2 and H4R3 on the PRMT5 target gene promoter and subsequently activating DVL3 expression and inhibiting expression of E-cadherin, RBL2, and miR-29b-1-5p. Moreover, miR-29b-1-5p was found to inversely regulate SMYD4 expression in HCC cells, thus forming a positive feedback loop. Furthermore, we found that the oncogenic effect of SMYD4 could be effectively suppressed by PRMT5 inhibitor in vitro and in vivo. Clinically, high coexpression of SMYD4 and PRMT5 was associated with poor prognosis of HCC patients. In summary, our study provides a model of crosstalk between lysine and arginine methyltransferases in HCC and highlights the SMYD4-PRMT5 axis as a potential therapeutic target for the treatment of HCC.

Indexed as

Carcinoma, HepatocellularCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticLiver NeoplasmsMicroRNAsProtein-Arginine N-MethyltransferasesAnimalsCell Line, TumorFeedback, PhysiologicalFemaleHistone-Lysine N-MethyltransferaseHumansMaleMethylationMiceHistone-Lysine N-MethyltransferaseMicroRNAsProtein-Arginine N-Methyltransferasesarginine methyltransferaseslysine methyltransferasesMEP50miR‐29b‐1‐5pPRMT5 inhibitor

Identifiers

PMID38438251
PMCPMC11093212
OpenAlexW4392375946

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.