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journal article·2025-10Open access

SNORA58 Facilitates Radioresistance via Suppressing JNK1‐Mediated Ferroptosis in Esophageal Squamous Cell Carcinoma

Yinli Zheng, Fangyi Liu, Yuhua Huang, Yanfen Feng, Xia Yang, Jinjun Wu, Xin Yang, Xuanhao Lin, Lives Jiang, Tingting Zeng, Yan Li, Xinyuan Guan, Yuanyuan Wang, Chunyan Chen, Jingping Yun

Advanced Science· Volume 12· Issue 40
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Source abstract

Abstract

Abstract Radioresistance represents a substantial challenge in cancer treatment, particularly in esophageal squamous cell carcinoma (ESCC), where the underlying molecular mechanisms remain incompletely understood. Small nucleolar RNAs (snoRNAs), primarily located in the nucleolus, are noncoding RNAs whose roles in ESCC radiotherapy are unclear. In this study, an upregulated snoRNA, SNORA58 is identified in ESCC via a snoRNA PCR array. Furthermore, based on multicenter data, SNORA58 is established as a promising biomarker for predicting response to neoadjuvant chemoradiotherapy (nCRT). Patients with high SNORA58 expression levels presented a lower likelihood of achieving a complete response to nCRT and poorer clinical outcomes. Functionally, SNORA58 enhances cancer cell resistance to radiotherapy without affecting chemotherapeutic sensitivity. Mechanistically, SNORA58 stabilizes CTCF by inhibiting its ubiquitin‐mediated degradation, leading to JNK1 downregulation and subsequent inactivation of the JNK signaling pathway; this disrupts intracellular iron homeostasis, thereby alleviating radiotherapy‐induced ferroptosis. Notably, the administration of a JNK signaling activator significantly restored the radiosensitivity of high‐SNORA58 ESCC cells both in vitro and in vivo. These findings elucidate the first demonstration of SNORA58 as a critical regulator of radioresistance in ESCC and reveal a novel link between snoRNAs and ferroptosis in this specific context, suggesting potential therapeutic strategies for managing ESCC.
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Research context

OpenAlex topics: RNA modifications and cancer · Cancer-related molecular mechanisms research · Ferroptosis and cancer prognosis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. China

Department of Pathology Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. China

Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China International Institute for Translational Chinese Medicine Guangzhou University of Chinese Medicine Guangzhou 510006 P. R. China

Department of Pathology National Cancer Center National Clinical Research Center for Cancer Cancer Hospital & Shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen 518000 P. R. China

Department of Pathology Shantou Central Hospital Shantou Guangdong 515041 P. R. China

Department of Pathology Affiliated Cancer Hospital and institute of Guangzhou Medical University Guangdong 510095 P. R. China

Department of Clinical Oncology State Key Laboratory for Liver Research The University of Hong Kong Hong Kong 852 P. R. China

Department of Clinical Oncology The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 P. R. China

Department of Radiology Oncology Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. China

Funding

National Natural Science Foundation of China · Guangdong Esophageal Cancer Research Institute · National Key Laboratory of Human Factors Engineering · Basic and Applied Basic Research Foundation of Guangdong Province

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