Work

RAD18 facilitates cancer progression and immunosuppression via the AKT/mTOR/c-Myc axis: a multi-omics analysis

Year: 2026

Type: article

Abstract: RAD18, a key E3 ubiquitin ligase implicated in DNA repair and genome stability, is tightly linked to cancer malignant progression, yet its pan-cancer prognostic and immunotherapeutic value remains poorly defined. Herein, we performed a comprehensive pan-cancer multi-omics analysis and validated the oncogenic mechanisms of RAD18 in liver hepatocellular carcinoma, pancreatic adenocarcinoma and triple-negative breast cancer via in vitro and in vivo assays. RAD18 was significantly overexpressed in 22 cancer types, associated with gene mutation, hypomethylation, poor prognosis and favorable diagnostic efficacy, serving as an independent poor prognostic factor for multiple cancers. Mechanistically, RAD18 promoted tumor proliferation, migration and immunosuppressive microenvironment remodeling by activating the AKT/mTOR/c-Myc axis and regulating TGF-β1/PD-L1 expression. Moreover, low RAD18 expression predicted a favorable response to immune checkpoint blockade therapy, while its high expression correlated with anti-PD-1 resistance in triple-negative breast cancer. Collectively, our findings identify RAD18 as a potential pan-cancer prognostic biomarker and immunotherapeutic target, with targeting RAD18 holding promise for reversing immunotherapy resistance in solid tumors.

Source: npj Precision Oncology

DOI: 10.1038/s41698-026-01468-0

Authors: Jinfeng Zhu, Qian Huang, Qingchun Liang, Wenjun Yi

Institutions: Changsha Medical University, Second Xiangya Hospital of Central South University, Tongji University, Shanghai East Hospital, Central South University

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,090