---
title: "JMJD5 enhances cisplatin sensitivity in NSCLC by increasing DNA damage"
id: "pubmed-42472515"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42472515"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42472515/"
doi: "10.1016/j.bbrc.2026.154270"
published_at: "2026-09-17T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# JMJD5 enhances cisplatin sensitivity in NSCLC by increasing DNA damage
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42472515
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42472515/)
- **DOI:** [10.1016/j.bbrc.2026.154270](https://doi.org/10.1016%2Fj.bbrc.2026.154270)
- **Published At:** 2026-09-17T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- JMJD5 (Jumonji Domain-Containing Protein 5) expression is associated with chemotherapy response in non‑small cell lung cancer (NSCLC); low JMJD5 correlates with worse overall survival in chemotherapy-treated patients and is downregulated after chemotherapy in tumor tissue. - In vitro, cisplatin reduces JMJD5 levels in NSCLC cell lines A549 and H1299. Restoring JMJD5 expression sensitizes these cells to cisplatin, reducing proliferation and colony formation while increasing apoptosis. - JMJD5 overexpression increases markers of **DNA damage**, notably elevated **γH2A.X**, indicating amplified DNA lesions following cisplatin exposure. - A catalytically inactive JMJD5 mutant retained the chemosensitizing effect, indicating the mechanism is **non-enzymatic**. - Mechanistic assays showed JMJD5 overexpression suppressed cisplatin-induced phosphorylation of Chk1 and Chk2, suggesting impaired checkpoint activation and reduced DNA damage response. - In nude mouse xenograft models, combining JMJD5 overexpression with cisplatin produced greater tumor growth inhibition than cisplatin alone, with reduced tumor volume and weight. - The authors propose JMJD5 as a potential target to overcome platinum resistance in NSCLC, supporting strategies to restore or stabilize JMJD5 expression in combination with standard platinum chemotherapy. - Details such as exact patient cohort sizes, specific doses, timepoints, and statistical values were not reported in the source abstract and would require consultation of the full text for confirmation.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 17. # JMJD5 promotes chemotherapy sensitivity of cisplatin in NSCLC by enhancing DNA damage [Jing He](https://pubmed.ncbi.nlm.nih.gov/?term=He+J&cauthor_id=42472515)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#full-view-affiliation-1 "School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China."), [Haohao Wei](https://pubmed.ncbi.nlm.nih.gov/?term=Wei+H&cauthor_id=42472515)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#full-view-affiliation-1 "School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China."), [Tao Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+T&cauthor_id=42472515)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#full-view-affiliation-2 "Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China."), [Qiuxiang Xiao](https://pubmed.ncbi.nlm.nih.gov/?term=Xiao+Q&cauthor_id=42472515)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#full-view-affiliation-3 "Department of Pathology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, China."), [Guiling Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+G&cauthor_id=42472515)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#full-view-affiliation-4 "School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China. Electronic address: lgling1996@gmu.edu.cn.") Affiliations Expand ### Affiliations * 1 School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China. * 2 Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China. * 3 Department of Pathology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, China. * 4 School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China. Electronic address: lgling1996@gmu.edu.cn. * PMID: **42472515** * DOI: [ 10.1016/j.bbrc.2026.154270 ](https://doi.org/10.1016/j.bbrc.2026.154270) Item in Clipboard # JMJD5 promotes chemotherapy sensitivity of cisplatin in NSCLC by enhancing DNA damage Jing He et al. Biochem Biophys Res Commun. 2026. Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42472515/) . 2026 Sep 17:831:154270. doi: 10.1016/j.bbrc.2026.154270. Epub 2026 Jul 17. ### Authors [Jing He](https://pubmed.ncbi.nlm.nih.gov/?term=He+J&cauthor_id=42472515)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#short-view-affiliation-1 "School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China."), [Haohao Wei](https://pubmed.ncbi.nlm.nih.gov/?term=Wei+H&cauthor_id=42472515)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#short-view-affiliation-1 "School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China."), [Tao Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+T&cauthor_id=42472515)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#short-view-affiliation-2 "Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China."), [Qiuxiang Xiao](https://pubmed.ncbi.nlm.nih.gov/?term=Xiao+Q&cauthor_id=42472515)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#short-view-affiliation-3 "Department of Pathology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, China."), [Guiling Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+G&cauthor_id=42472515)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42472515/#short-view-affiliation-4 "School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China. Electronic address: lgling1996@gmu.edu.cn.") ### Affiliations * 1 School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China. * 2 Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China. * 3 Department of Pathology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, China. * 4 School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China. Electronic address: lgling1996@gmu.edu.cn. * PMID: **42472515** * DOI: [ 10.1016/j.bbrc.2026.154270 ](https://doi.org/10.1016/j.bbrc.2026.154270) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Platinum-based chemotherapy remains a cornerstone in the treatment of advanced non-small cell lung cancer (NSCLC), yet its efficacy is frequently limited by drug resistance. JMJD5 (Jumonji Domain-Containing Protein 5) is a multifunctional protein implicated in tumor progression with enzymatic and non-enzymatic activities. While it has been reported to enhance the sensitivity of NSCLC cells to EGFR tyrosine kinase inhibitors (TKIs), its function in modulating response to conventional platinum chemotherapy is unknown. **Methods:** The clinical relevance of JMJD5 was assessed via bioinformatics analysis of patient cohorts. In vitro functional assays in A549 and H1299 cells included overexpression modeling, cytotoxicity and colony formation, apoptosis analysis, and DNA damage assessment. An enzymatically inactive JMJD5 mutant was employed to dissect mechanism. The synergistic anti-tumor effect was validated in nude mouse xenograft models. **Results:** Low JMJD5 expression correlated with poorer overall survival in chemotherapy-treated NSCLC patients and was downregulated in tumor tissues post-chemotherapy. Cisplatin treatment reduced JMJD5 levels in vitro. Restoring JMJD5 expression significantly sensitized cells to cisplatin, enhancing its anti-proliferative and pro-apoptotic effects. This was associated with augmented DNA damage, evidenced by elevated γH2A.X. Crucially, the chemosensitizing function was independent of JMJD5's enzymatic activity. Mechanistically, JMJD5 overexpression suppressed cisplatin-induced Chk1/Chk2 phosphorylation, indicating impaired checkpoint activation. In vivo, JMJD5 overexpression combined with cisplatin markedly suppressed tumor growth, reducing both tumor volume and weight compared to cisplatin alone. **Conclusions:** Our results demonstrate that JMJD5 enhances cisplatin sensitivity in NSCLC by amplifying DNA damage and apoptosis through a non-catalytic mechanism. JMJD5 thus represents a novel potential target for overcoming platinum resistance, offering a rationale for therapeutic strategies aimed at restoring or stabilizing its expression in combination with conventional chemotherapy. **Keywords:** Chemosensitivity; Cisplatin; DNA damage; JMJD5; NSCLC. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Yifei Sanjie pill combined with gefitinib reduces the progression of EGFR-TKIs-resistant non-small cell lung cancer via YAP/ANKRD1 axis. ](https://pubmed.ncbi.nlm.nih.gov/41865688/) Yuan Y, Zhou R, Ye Z, Yang L, Gao T, Xu H, Tang X, Wu D, Li J, Lin Z, Luo Y, Qin B, Li L, Zheng C, Zhang J, Tang Y, Lin L.Yuan Y, et al.Phytomedicine. 2026 Jun;155:158003. doi: 10.1016/j.phymed.2026.158003. Epub 2026 Feb 23.Phytomedicine. 2026.PMID: 41865688 * [ TRIM46 deficiency‑induced DNA damage enhances the sensitivity of cisplatin in non‑small cell lung cancer by regulating the Akt signaling pathway. ](https://pubmed.ncbi.nlm.nih.gov/41614410/) Jin S, Zhang D, Liao Z, Yu L, Wang Y, Jia P, Pan M, Li Y, Zhang J.Jin S, et al.Oncol Rep. 2026 Apr;55(4):58. doi: 10.3892/or.2026.9063. Epub 2026 Jan 30.Oncol Rep. 2026.PMID: 41614410Free PMC article. * [ Narciclasine enhances cisplatin-induced apoptotic cell death by inducing unfolded protein response-mediated regulation of NOXA and MCL1. ](https://pubmed.ncbi.nlm.nih.gov/40369444/) Lee JH, Seo SH, Shim J, Kim YN, Yoon K.Lee JH, et al.Cell Mol Biol Lett. 2025 May 14;30(1):59. doi: 10.1186/s11658-025-00735-5.Cell Mol Biol Lett. 2025.PMID: 40369444Free PMC article. * [ The dual PI3K/mTOR inhibitor BEZ235 restricts the growth of lung cancer tumors regardless of EGFR status, as a potent accompanist in combined therapeutic regimens. ](https://pubmed.ncbi.nlm.nih.gov/31262325/) Wu YY, Wu HC, Wu JE, Huang KY, Yang SC, Chen SX, Tsao CJ, Hsu KF, Chen YL, Hong TM.Wu YY, et al.J Exp Clin Cancer Res. 2019 Jul 1;38(1):282. doi: 10.1186/s13046-019-1282-0.J Exp Clin Cancer Res. 2019.PMID: 31262325Free PMC article. * [ Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. ](https://pubmed.ncbi.nlm.nih.gov/21435938/) Murphy M, Stordal B.Murphy M, et al.Drug Resist Updat. 2011 Jun;14(3):177-90. doi: 10.1016/j.drup.2011.02.004. 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