Unraveling the role of RDM1 in head and neck squamous cell carcinoma: insights into DDR regulation and antioxidant response
4 affiliations
- 1Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
- 2Department of Geriatrics, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
- 3Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
- 4Department of Otolaryngology Guangdong Provincial Key Laboratory of Intelligent Port Security Inspection, Guangzhou, Guangdong, China
Abstract
Advanced Head and Neck Squamous Cell Carcinomas (HNSCCs) pose a significant clinical challenge due to their poor survival rates. The DNA damage response (DDR) pathway plays a crucial role in the progression and treatment of advanced HNSCC, prompting the need to identify the underlying molecular mechanisms and develop innovative therapeutic strategies. One promising candidate is the RAD52 motif-containing protein 1 (RDM1), which functions as a regulator of DDR and exhibits context-dependent roles in tumorigenesis. However, the precise function and molecular mechanism of RDM1 in HNSCC remain poorly understood. In our study, we observed a relatively high expression of RDM1 in HNSCC tumor tissues. Functional experiments revealed that RDM1 contributed to increased cell proliferation and suppressed apoptosis in HNSCC cells, indicating its oncogenic role in HNSCC development. By modulating the levels of RAD52/TP53 and CDKN1A/CDK6 proteins, RDM1 played a critical role in regulating DDR and the cell cycle in HNSCC cells. Additionally, our investigations uncovered a novel role of RDM1 in the antioxidant response, wherein it facilitated the accumulation of NRF2 proteins. Interestingly, we found that RDM1 interacted with KEAP1 protein to promote NRF2 accumulation, ultimately promoting HNSCC progression. These findings establish the oncogenic role of RDM1 in HNSCC and emphasize the novel RDM1-KEAP1-NRF2 axis as a mechanism underlying the antioxidant response. They also highlight the potential of RDM1 as a therapeutic target for HNSCC, while its prognostic value warrants further validation in larger independent cohorts.
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BibTeX
@article{wang2026unraveling,
title = {{Unraveling the role of RDM1 in head and neck squamous cell carcinoma: insights into DDR regulation and antioxidant response}},
author = {Fengpin Wang and Jie Wu and Wenjie Wang and Ruilin Zhao and Yunqi Mao and Fuhan Wu and Yixuan Li and Pingjiang Ge and Weiqun Zhu and Xiaodong Yan and Yanfang Zheng and Zhongming Lu},
journal = {Frontiers in Molecular Biosciences},
year = {2026},
month = oct,
doi = {10.3389/fmolb.2026.1944888},
url = {https://doi.org/10.3389/fmolb.2026.1944888},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Unraveling the role of RDM1 in head and neck squamous cell carcinoma: insights into DDR regulation and antioxidant response
AU - Fengpin Wang
AU - Jie Wu
AU - Wenjie Wang
AU - Ruilin Zhao
AU - Yunqi Mao
AU - Fuhan Wu
AU - Yixuan Li
AU - Pingjiang Ge
AU - Weiqun Zhu
AU - Xiaodong Yan
AU - Yanfang Zheng
AU - Zhongming Lu
PY - 2026
DA - 2026/10/13
JO - Frontiers in Molecular Biosciences
DO - 10.3389/fmolb.2026.1944888
UR - https://doi.org/10.3389/fmolb.2026.1944888
AB - Advanced Head and Neck Squamous Cell Carcinomas (HNSCCs) pose a significant clinical challenge due to their poor survival rates. The DNA damage response (DDR) pathway plays a crucial role in the progression and treatment of advanced HNSCC, prompting the need to identify the underlying molecular mechanisms and develop innovative therapeutic strategies. One promising candidate is the RAD52 motif-containing protein 1 (RDM1), which functions as a regulator of DDR and exhibits context-dependent roles in tumorigenesis. However, the precise function and molecular mechanism of RDM1 in HNSCC remain poorly understood. In our study, we observed a relatively high expression of RDM1 in HNSCC tumor tissues. Functional experiments revealed that RDM1 contributed to increased cell proliferation and suppressed apoptosis in HNSCC cells, indicating its oncogenic role in HNSCC development. By modulating the levels of RAD52/TP53 and CDKN1A/CDK6 proteins, RDM1 played a critical role in regulating DDR and the cell cycle in HNSCC cells. Additionally, our investigations uncovered a novel role of RDM1 in the antioxidant response, wherein it facilitated the accumulation of NRF2 proteins. Interestingly, we found that RDM1 interacted with KEAP1 protein to promote NRF2 accumulation, ultimately promoting HNSCC progression. These findings establish the oncogenic role of RDM1 in HNSCC and emphasize the novel RDM1-KEAP1-NRF2 axis as a mechanism underlying the antioxidant response. They also highlight the potential of RDM1 as a therapeutic target for HNSCC, while its prognostic value warrants further validation in larger independent cohorts.
SN - 2296-889X
ER -