Evidence map›Paper›PMID 41254727›Full record

ArticleEuropean journal of medical research2025

RNF185 promotes esophageal squamous cell carcinoma progression by regulating BAK1 ubiquitination and activating the cGAS-STING-IRF3 pathway.

Ke-Hao Wang, Hui Zhu, Meng-Dan Xu, Yi-Ping Wang, Qing-Qing Fan, Dan-Ping Cen, Shu-Jun Wang

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Article in European journal of medical research, 2025. 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
–field-weighted citation impact
1 · What the graph read from it

What it found

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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.

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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

7 authors.

Ke-Hao Wang *Cixi People's Hospital Medical Health Group (Cixi People's Hospital), Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, China.
Hui Zhu *Cixi People's Hospital Medical Health Group (Cixi People's Hospital), Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, China.
Meng-Dan XuCixi People's Hospital Medical Health Group (Cixi People's Hospital), Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, China.
Yi-Ping WangCixi People's Hospital Medical Health Group (Cixi People's Hospital), Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, China.
Qing-Qing FanCixi People's Hospital Medical Health Group (Cixi People's Hospital), Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, China.
Dan-Ping CenCixi People's Hospital Medical Health Group (Cixi People's Hospital), Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, China.
Shu-Jun WangCixi People's Hospital Medical Health Group (Cixi People's Hospital), Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, China. m13429332988@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveRNF185 is a mitochondrial RING-type E3 ubiquitin ligase known to regulate mitochondrial homeostasis, apoptosis, and innate immune signaling through ubiquitination of substrates such as BNIP1, JWA, and cGAS. Although dysregulation of RNF185 has been reported in several cancers, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. The present study aimed to investigate the function of RNF185 in ESCC progression and assess its potential as a therapeutic target.

methodsWe analyzed RNF185 expression in the TCGA-ESCA dataset and ESCC cell lines. RNF185 knockout cell lines were generated using CRISPR/Cas9. Functional assays including CCK-8, colony formation, apoptosis analysis, transmission electron microscopy (TEM), and ELISA were performed. Activation of the cGAS-STING pathway and downstream transcription factors was assessed by Western blot, qPCR, luciferase assays, and ChIP-qPCR. BAK1 ubiquitination and interaction with RNF185 were evaluated using immunoprecipitation. In vivo tumor growth inhibition was tested using a subcutaneous mouse xenograft model with Honokiol treatment.

resultsRNF185 was significantly overexpressed in ESCC tissues and correlated with worse patient outcomes. RNF185 knockout suppressed cell proliferation, induced apoptosis, and caused mitochondrial damage and mtDNA release, activating the cGAS-STING-IRF3 pathway. Mechanistically, RNF185 mediated BAK1 ubiquitination to maintain mitochondrial integrity. Loss of RNF185 led to BAK1 accumulation and IRF3-dependent transcriptional upregulation of BAK1, forming a positive feedback loop promoting apoptosis. Knockdown of BAK1 or IRF3 rescued mitochondrial structure and cell survival. Honokiol, identified via molecular docking, targeted RNF185, reduced BAK1 ubiquitination, activated innate immune signaling, and inhibited tumor growth in vivo.

conclusionRNF185 sustains mitochondrial homeostasis and ESCC cell survival by promoting BAK1 ubiquitination and limiting cGAS-STING-IRF3-mediated immune activation. Targeting RNF185 with small molecules like Honokiol may represent a promising therapeutic approach in ESCC.

Indexed as

bcl-2 Homologous Antagonist-Killer ProteinEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaInterferon Regulatory Factor-3Membrane ProteinsNucleotidyltransferasesUbiquitin-Protein LigasesAnimalsApoptosisCell Line, TumorCell ProliferationCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDisease ProgressionGene Expression Regulation, NeoplasticHumansMiceBAK1 protein, humanbcl-2 Homologous Antagonist-Killer ProteincGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseInterferon Regulatory Factor-3IRF3 protein, humanMembrane ProteinsNucleotidyltransferasesSTING1 protein, humanSTING ProteinUbiquitin-Protein LigasesBAK1 ubiquitinationCGAS–STING pathwayEsophageal squamous cell carcinoma (ESCC)Mitochondrial apoptosisRNF185

Identifiers

PMID41254727
PMCPMC12628518

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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.