Evidence map›Paper›PMID 42138474›Full record

ArticleClinical and translational medicine2026

TMEM92 shields DDX3X from TTC3-mediated degradation to confer chemoresistance in triple-negative breast cancer.

Hao Shen, Xiaochao Jia, Xu Li, Zhi Li, Zhihua Zhang, Yang Zhao, Lei Shen, Xiaoqiu Bu, Qiang Ma, Chunli Liang and 3 more

Abstract read
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Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

13 authors.

Hao ShenDepartment of Thyroid Breast Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiaochao JiaDepartment of Medical Ultrasound, Jinshan Hospital of Fudan University, Shanghai, China.
Xu LiCenter of Hepatobiliary Pancreatic Disease, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
Zhi LiDepartment of Breast and Thyroid Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
Zhihua ZhangDepartment of Medical Ultrasound, Jinshan Hospital of Fudan University, Shanghai, China.
Yang ZhaoDepartment of Medical Ultrasound, Jinshan Hospital of Fudan University, Shanghai, China.
Lei ShenDepartment of Thyroid Breast Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiaoqiu BuDepartment of Thyroid Breast Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Qiang MaDepartment of Thyroid Breast Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Chunli LiangDepartment of Thyroid Breast Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiaoti LinDepartment of Thyroid Breast Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Lin-Xiaoxi MaDepartment of Breast Surgery, Fudan University Shanghai Cancer Center, Key Laboratory of Breast Cancer in Shanghai, Shanghai, China.
Chuan QinDepartment of Medical Ultrasound, Jinshan Hospital of Fudan University, Shanghai, China.

Funding

Natural Science Research Program of Huai'an, Jiangsu, China HAB202301Scientific Research Program of the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University YCT202302Shanghai Municipal Health Commission Scientific Research Project 202340204The Seventh Cycle of Key Medical Specialties in Jinshan District-Ultrasound Department (Back-up Category) JSZK2023H02The Wu Jieping Medical Foundation 320.6750.2023-18-82Three-Year Action Plan for Talent Team Construction (2023-2025) Implementation Plan of Jinshan Hospital Affiliated to Fudan University, there is a key development discipline cluster construction project-the Department of Ultrasonic Medicine ZDXK-2025-4
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) remains a major clinical challenge because of its aggressive characteristics, limited targeted treatment options, and frequent chemoresistance. However, the molecular mechanisms governing protein stability that drive TNBC progression and therapeutic resistance remain incompletely understood.

methodsTMEM92 expression and clinical relevance were evaluated using public datasets, patient specimens, and TNBC cell models. Loss-of-function, rescue, xenograft, protein interaction, and ubiquitination assays were performed to determine the biological function and molecular mechanism of TMEM92 in TNBC progression and cisplatin response.

resultsTMEM92 was prominently expressed in TNBC and correlated with poor prognosis. Functionally, depletion of TMEM92 suppressed TNBC cell proliferation, migration, invasion, and survival while promoting apoptosis in vitro and in vivo. Mechanistically, TMEM92 directly associated with DEAD-box helicase 3 X-linked (DDX3X) and protected it from degradation by the E3 ubiquitin ligase tetratricopeptide repeat domain 3 (TTC3). TMEM92 competitively prevented TTC3 binding to DDX3X, thereby inhibiting TTC3-mediated K48-linked ubiquitination and subsequent proteasomal degradation of DDX3X. Re-expression of DDX3X rescued the anti-tumor effects induced by TMEM92 knockdown. Therapeutically, TMEM92 targeting sensitized TNBC cells and xenograft tumors to cisplatin. TMEM92 knockout reduced the cisplatin IC

conclusionsThis study identifies a novel TMEM92DDX3XTTC3 axis that regulates DDX3X protein stability and drives TNBC progression and chemoresistance, revealing a potential prognostic and therapeutic vulnerability in TNBC.

Indexed as

DEAD-box RNA HelicasesDrug Resistance, NeoplasmMembrane ProteinsTriple Negative Breast NeoplasmsAnimalsCell Line, TumorCisplatinFemaleHumansMiceProteolysisCisplatinDDX3X protein, humanDEAD-box RNA HelicasesMembrane Proteinscisplatin resistanceDDX3XTMEM92triple‐negative breast cancerTTC3ubiquitination

Identifiers

PMID42138474
PMCPMC13178151

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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.