2. Academic Validation
  3. RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis

RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis

  • Int J Surg. 2024 Oct 1. doi: 10.1097/JS9.0000000000002099.
Qingqing Xu 1 2 3,  Xin Wen 4,  Chenglong Huang 1 2 3,  Zaishan Lin 1 2 3,  Zhen Xu 1 2 3,  Ciming Sun 1 2 3,  Li Li 1 2 3,  Suixian Zhang 1 2 3,  Shuanghong Song 1 2 3,  Jiahao Lou 1 2 3,  Zan Hou 1 2 3,  Yuanyuan Chen 1 2 3,  Xuan Li 1 2 3,  Lei Chen 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
  • 2 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
  • 3 United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co, Guangzhou, 510060, China.
  • 4 Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
PMID: 39352125 DOI: 10.1097/JS9.0000000000002099
Abstract

Background: Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, Apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown.

Methods: RNA Sequencing and bioinformatic analysis were used to determine the potential function of RRFERV (radiation-resistant but Ferroptosis vulnerable), and its biological effects were investigated using in vitro and in vivo experiments. Western blotting, quantitative real-time Reverse transcription PCR, RNA immunoprecipitation (RIP) assays, and flow cytometry detected RRFERV expression. Ferroptosis and lipid peroxidation were added to evaluate the relationship between it and radiotherapy resistance.

Results: LncRNA-RRFERV was both highly expressed in NPC tissues and radiation-resistant cells. RRFERV is associated with poor clinical outcomes of NPC patients and stabilizes TEAD1 by competitive binding with microRNA-615-5p and microRNA-1293. RRFERV-TEAD1 signaling axis leads to malignant progression and radiotherapy resistance of NPC. Furthermore, we observed that NPC radiotherapy resistance cells exist in a fragile oxidative stress equilibrium, which makes them more sensitive to Ferroptosis inducers. Surprisingly, we found that RRFERV-TEAD1 signaling axis also plays a key role in mediating the lipid peroxidation levels of NPC radiotherapy resistance cells through transcriptional activation of ACSL4/TFRC.

Conclusions: RRFERV serves as an independent prognostic factor in NPC. During the malignant progression of NPC caused by high expression of RRFERV, Ferroptosis can be induced to effectively kill Cancer cells and reverse the radiotherapy resistance of NPC cells, suggesting a potential treatment approach for recurrent and refractory NPC.

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