Evidence map›Paper›PMID 37199893›Full record

ArticleMolecular and cellular biochemistry2024

Pharmacological inhibition of EZH2 using a covalent inhibitor suppresses human ovarian cancer cell migration and invasion.

Lihong Shi, Qiangsheng Zhang, Shirui Zhu, Qing Tang, Xin Chen, Rui Lan, Ningyu Wang, Yongxia Zhu

Abstract read
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In one paragraph

Article in Molecular and cellular biochemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
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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

8 authors at 4 institutions in 1 country.

Lihong ShiDepartment of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610041, China.
Qiangsheng ZhangDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Shirui ZhuDepartment of Encephalopathy, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Qing TangSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
Xin ChenSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
Rui LanDepartment of Encephalopathy, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Ningyu WangSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
Yongxia ZhuDepartment of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610041, China. yongxia_zhu0409@uestc.edu.cn.
Southwest Jiaotong University · CNFirst Affiliated Hospital of Henan University · CNUniversity of Electronic Science and Technology of China · CNSichuan University · CN

Funding

China International Medical Foundation Z-2021-46-2101Excellent Youth Fund of Sichuan Cancer Hospital YB2021024Scientific research project of Sichuan Medical S20023
6 · The paper itself

Abstract

Metastasis is the cause of poor prognosis in ovarian cancer (OC). Enhancer of Zeste homolog 2 (EZH2), a histone-lysine N-methyltransferase enzyme, promotes OC cell migration and invasion by regulating the expression of tissue inhibitor of metalloproteinase-2 (TIMP2) and matrix metalloproteinases-9 (MMP9). Hence, we speculated that EZH2-targeting therapy might suppress OC migration and invasion. In this study, the expression of EZH2, TIMP2, and MMP9 in OC tissues and cell lines was analyzed using The Cancer Genome Atlas (TCGA) database and western blotting, respectively. The effects of SKLB-03220, an EZH2 covalent inhibitor, on OC cell migration and invasion were investigated using wound-healing assays, Transwell assays, and immunohistochemistry. TCGA database analysis confirmed that the EZH2 and MMP9 mRNA expression was significantly higher in OC tissues, whereas TIMP2 expression was significantly lower than that in normal ovarian tissues. Moreover, EZH2 negatively correlated with TIMP2 and positively correlated with MMP9 expression. In addition to the anti-tumor activity of SKLB-03220 in a PA-1 xenograft model, immunohistochemistry results showed that SKLB-03220 markedly increased the expression of TIMP2 and decreased the expression of MMP9. Additionally, wound-healing and Transwell assays showed that SKLB-03220 significantly inhibited the migration and invasion of both A2780 and PA-1 cells in a concentration-dependent manner. SKLB-03220 inhibited H3K27me3 and MMP9 expression and increased TIMP2 expression in PA-1 cells. Taken together, these results indicate that the EZH2 covalent inhibitor SKLB-03220 inhibits metastasis of OC cells by upregulating TIMP2 and downregulating MMP9, and could thus serve as a therapeutic agent for OC.

Indexed as

AcrylamidesEnhancer of Zeste Homolog 2 ProteinOvarian NeoplasmsCell Line, TumorCell MovementCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMatrix Metalloproteinase 9Tissue Inhibitor of Metalloproteinase-2AcrylamidesEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanMatrix Metalloproteinase 9SKLB-03220Tissue Inhibitor of Metalloproteinase-2Covalent inhibitorEnhancer of Zeste homolog 2MetastasisOvarian cancer

Identifiers

PMID37199893
OpenAlexW4377011995

What OpenQuestion holds

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Registered trials

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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.