---
title: "JMJD6 in Cancer: Mechanisms Driving Oncogenesis and Immune Evasion"
id: "pubmed-42361741"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42361741"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42361741/"
doi: "10.1016/j.bbrc.2026.154198"
published_at: "2026-09-03T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# JMJD6 in Cancer: Mechanisms Driving Oncogenesis and Immune Evasion
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42361741
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42361741/)
- **DOI:** [10.1016/j.bbrc.2026.154198](https://doi.org/10.1016%2Fj.bbrc.2026.154198)
- **Published At:** 2026-09-03T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- JMJD6 is an Fe2+- and α-ketoglutarate–dependent dioxygenase with multiple enzymatic activities that regulate epigenetic and post-transcriptional processes. - The enzyme is frequently **overexpressed** across diverse malignancies and is associated with poorer patient prognosis according to the source review. - JMJD6 promotes tumor cell–intrinsic programs including **proliferation**, **invasion**, **metastasis**, and maintenance of **stemness**. - Mechanistic actions described include **p53 hydroxylation** and activation of the **β-catenin/c-Myc** signaling axis, linking JMJD6 activity to classic oncogenic pathways. - JMJD6 also shapes the tumor microenvironment to favor immune suppression and **tumor immune evasion**, for example by promoting M2-type tumor-associated macrophage polarization via the **STAT3/IL-10** axis. - The enzyme thus functions as a molecular bridge between internal oncogenic programs and extrinsic immunosuppressive conditions in tumors. - Given these roles, JMJD6 is highlighted as a promising prognostic **biomarker** and a potential **therapeutic target**. - The review summarizes recent developments in **JMJD6-targeted small-molecule inhibitors** and proposes combining JMJD6 inhibition with **immune checkpoint inhibitors** as an experimental therapeutic strategy. - The authors note this combined targeting approach remains preliminary and requires further investigation; current challenges and directions for clinical translation are discussed in the source. - The review declares no conflicts of interest.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jun 24. # Dual roles of JMJD6 in oncogenesis and immune evasion: molecular mechanisms and therapeutic prospects [Si-Yuan Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+SY&cauthor_id=42361741)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#full-view-affiliation-1 "Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China."), [Jing Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+J&cauthor_id=42361741)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#full-view-affiliation-1 "Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China."), [Xiao-Mo Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+XM&cauthor_id=42361741)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#full-view-affiliation-2 "College of Pediatrics, Chongqing Medical University, Chongqing, 400016, China."), [Man-Ni Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+MN&cauthor_id=42361741)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#full-view-affiliation-3 "Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China."), [Hai-Xia Hao](https://pubmed.ncbi.nlm.nih.gov/?term=Hao+HX&cauthor_id=42361741)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#full-view-affiliation-4 "Department of Clinical Laboratory, Sinopharm Tongmei General Hospital, Datong, 037000, China."), [Qin Zheng](https://pubmed.ncbi.nlm.nih.gov/?term=Zheng+Q&cauthor_id=42361741)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#full-view-affiliation-5 "Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China. Electronic address: zhengqinhx@scu.edu.cn.") Affiliations Expand ### Affiliations * 1 Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China. * 2 College of Pediatrics, Chongqing Medical University, Chongqing, 400016, China. * 3 Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China. * 4 Department of Clinical Laboratory, Sinopharm Tongmei General Hospital, Datong, 037000, China. * 5 Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China. Electronic address: zhengqinhx@scu.edu.cn. * PMID: **42361741** * DOI: [ 10.1016/j.bbrc.2026.154198 ](https://doi.org/10.1016/j.bbrc.2026.154198) Item in Clipboard Review # Dual roles of JMJD6 in oncogenesis and immune evasion: molecular mechanisms and therapeutic prospects Si-Yuan Chen 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/42361741/) . 2026 Sep 3:829:154198. doi: 10.1016/j.bbrc.2026.154198. Epub 2026 Jun 24. ### Authors [Si-Yuan Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+SY&cauthor_id=42361741)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#short-view-affiliation-1 "Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China."), [Jing Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+J&cauthor_id=42361741)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#short-view-affiliation-1 "Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China."), [Xiao-Mo Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+XM&cauthor_id=42361741)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#short-view-affiliation-2 "College of Pediatrics, Chongqing Medical University, Chongqing, 400016, China."), [Man-Ni Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+MN&cauthor_id=42361741)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#short-view-affiliation-3 "Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China."), [Hai-Xia Hao](https://pubmed.ncbi.nlm.nih.gov/?term=Hao+HX&cauthor_id=42361741)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#short-view-affiliation-4 "Department of Clinical Laboratory, Sinopharm Tongmei General Hospital, Datong, 037000, China."), [Qin Zheng](https://pubmed.ncbi.nlm.nih.gov/?term=Zheng+Q&cauthor_id=42361741)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42361741/#short-view-affiliation-5 "Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China. Electronic address: zhengqinhx@scu.edu.cn.") ### Affiliations * 1 Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China. * 2 College of Pediatrics, Chongqing Medical University, Chongqing, 400016, China. * 3 Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China. * 4 Department of Clinical Laboratory, Sinopharm Tongmei General Hospital, Datong, 037000, China. * 5 Department of Laboratory Medicine, West China Hospital of Sichuan University, Sichuan Clinical Research Center for Laboratory Medicine, Clinical Laboratory Medicine Research Center of West China Hospital, Chengdu, 610041, China. Electronic address: zhengqinhx@scu.edu.cn. * PMID: **42361741** * DOI: [ 10.1016/j.bbrc.2026.154198 ](https://doi.org/10.1016/j.bbrc.2026.154198) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract JMJD6 is an iron (Fe2+)- and α-ketoglutarate (2-OG)-dependent dioxygenase that exhibits multiple enzymatic activities. As a key regulator of epigenetic and post-transcriptional processes, JMJD6 is frequently overexpressed in various malignancies and is closely associated with poor patient prognosis. This review systematically examines the central role of JMJD6 in tumorigenesis and cancer progression. Specifically, JMJD6 directly promotes tumor cell proliferation, invasion, metastasis, and stemness maintenance through mechanisms such as p53 hydroxylation and activation of the β-catenin/c-Myc signaling pathway. Furthermore, JMJD6 actively influences the immunosuppressive tumor microenvironment that facilitates tumor immune evasion, for example, by promoting M2-type tumor-associated macrophage polarization through the STAT3/IL-10 axis. Consequently, JMJD6 emerges as a multifunctional enzyme connecting intrinsic oncogenic programs with extrinsic immunosuppressive microenvironments. Given its pivotal roles, JMJD6 has become a promising prognostic biomarker and therapeutic target. Targeting JMJD6, particularly in combination with immune checkpoint inhibitors, represents a promising but still experimental strategy that warrants further investigation. This review further summarizes recent advances in JMJD6-targeted small-molecule inhibitors and combination therapy strategies, while discussing current challenges and future directions for clinical translation. **Keywords:** Epigenetic modification; Immunotherapy; JMJD6; Oncogenesis; Targeted therapy; Tumor microenvironment. 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 there is no conflict of interest. ## Similar articles * [ JMJD6 in tumor-associated macrophage regulates macrophage polarization and cancer progression via STAT3/IL-10 axis. ](https://pubmed.ncbi.nlm.nih.gov/37567973/) Chen S, Wang M, Lu T, Liu Y, Hong W, He X, Cheng Y, Liu J, Wei Y, Wei X.Chen S, et al.Oncogene. 2023 Sep;42(37):2737-2750. doi: 10.1038/s41388-023-02781-9. Epub 2023 Aug 11.Oncogene. 2023.PMID: 37567973Free PMC article. * [ JMJD6 promotes colon carcinogenesis through negative regulation of p53 by hydroxylation. ](https://pubmed.ncbi.nlm.nih.gov/24667498/) Wang F, He L, Huangyang P, Liang J, Si W, Yan R, Han X, Liu S, Gui B, Li W, Miao D, Jing C, Liu Z, Pei F, Sun L, Shang Y.Wang F, et al.PLoS Biol. 2014 Mar 25;12(3):e1001819. doi: 10.1371/journal.pbio.1001819. eCollection 2014 Mar.PLoS Biol. 2014.PMID: 24667498Free PMC article. * [ Role of the Epigenetic Modifier JMJD6 in Tumor Development and Regulation of Immune Response. ](https://pubmed.ncbi.nlm.nih.gov/35359945/) Wang K, Yang C, Li H, Liu X, Zheng M, Xuan Z, Mei Z, Wang H.Wang K, et al.Front Immunol. 2022 Mar 14;13:859893. doi: 10.3389/fimmu.2022.859893. eCollection 2022.Front Immunol. 2022.PMID: 35359945Free PMC article.Review. * [ The epigenetic modifier JMJD6 is amplified in mammary tumors and cooperates with c-Myc to enhance cellular transformation, tumor progression, and metastasis. ](https://pubmed.ncbi.nlm.nih.gov/27081402/) Aprelikova O, Chen K, El Touny LH, Brignatz-Guittard C, Han J, Qiu T, Yang HH, Lee MP, Zhu M, Green JE.Aprelikova O, et al.Clin Epigenetics. 2016 Apr 14;8:38. doi: 10.1186/s13148-016-0205-6. eCollection 2016.Clin Epigenetics. 2016.PMID: 27081402Free PMC article. * [ Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy. ](https://pubmed.ncbi.nlm.nih.gov/39893129/) Thuya WL, Cao Y, Ho PC, Wong AL, Wang L, Zhou J, Nicot C, Goh BC.Thuya WL, et al.Cytokine Growth Factor Rev. 2025 Oct;85:26-42. doi: 10.1016/j.cytogfr.2025.01.003. Epub 2025 Jan 17.Cytokine Growth Factor Rev. 2025.PMID: 39893129Review. 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