Evidence map›Paper›PMID 41114773›Full record

ArticleCell biology and toxicology2025

ETV4 promotes ovarian cancer growth by regulating mitochondrial function through Mfn2 ubiquitination mediated by the E3 ubiquitin ligase MARCH9.

Ying Wang, Zhan Wang, Juan Chen, Li Cai, Xia Luo, Nayiyuan Wu

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Article in Cell biology and toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Ying WangDepartment of the Central Laboratory, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, Hunan, People's Republic of China. wangying2479@hnca.org.cn.
Zhan WangLung Cancer and Gastrointestinal Unit, Department of Medical Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410031, P. R. China.
Juan ChenDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, P. R. China.
Li CaiDali University, Dali, Yunnan, P. R. China.
Xia LuoDepartment of the Central Laboratory, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, Hunan, People's Republic of China.
Nayiyuan WuDepartment of the Central Laboratory, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, Hunan, People's Republic of China.

Funding

Natural Science Foundation of Hunan Province 2023JJ60333
6 · The paper itself

Abstract

backgroundMitochondrial dysfunction affects the development of ovarian cancer (OC). ETV4 is involved in mitochondrial fusion. The regulatory pathways of ETV4 in OC cells have not been further investigated. In this study, we aimed to explore the effects of ETV4 on OC development and analyze the downstream regulatory pathways of ETV4.

methodsThe expression of ETV4 in OC cell lines (SK-OV-3, HEY, A2780, and OVCAR-3) was verified. After silencing ETV4, indicators related to mitochondrial function, including ATP level, mitochondrial membrane potential, mitochondrial DNA (mtDNA), and mitochondrial ROS (mtROS), were analyzed. The expression of mitochondrial fission/fusion-related markers (Mfn1, Mfn2, OPA1, DRP1, MFF, and FIS1) was detected. In vivo experiments were used to verify the effect of ETV4 on OC development.

resultsThe TCGA-OV data indicated that ETV4 was highly expressed in OC. Silencing ETV4 inhibited the proliferation of OC cells. Mitochondrial membrane potential and ATP levels increased after ETV4 silencing, while mtDNA and mtROS levels decreased. ETV4 silencing promoted Mfn2 protein expression but did not affect Mfn2 mRNA level. Mfn2-associated E3 ubiquitin ligase MARCH9 was targeted and regulated by ETV4. MARCH9 overexpression alleviated the regulation of ETV4 silencing on mitochondrial function in OC cells. Lysosomal inhibitor CQ blocked the degradation of ubiquitinated Mfn2 protein. MARCH9 was found to mediate robust ubiquitination of Mfn2 via the K63-linked ubiquitination.

conclusionsETV4 was highly expressed in OC and involved in the regulation of mitochondrial function. ETV4 regulated Mfn2 ubiquitination linked by K63 by regulating MARCH9.

Indexed as

GTP PhosphohydrolasesMembrane ProteinsMitochondriaMitochondrial ProteinsOvarian NeoplasmsProto-Oncogene ProteinsProto-Oncogene Proteins c-etsUbiquitin-Protein LigasesAnimalsCell Line, TumorCell ProliferationDNA, MitochondrialFemaleHumansMembrane Potential, MitochondrialMiceDNA, MitochondrialETV4 protein, humanGTP PhosphohydrolasesMembrane ProteinsMFN2 protein, humanMitochondrial ProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-etsReactive Oxygen SpeciesUbiquitin-Protein LigasesETV4MARCH9Mfn2Mitochondrial functionOvarian cancer (OC)

Identifiers

PMID41114773
PMCPMC12537605

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