1. Academic Validation
  2. CircCDYL promotes glycolysis to drive the progression of nasopharyngeal carcinoma

CircCDYL promotes glycolysis to drive the progression of nasopharyngeal carcinoma

  • J Adv Res. 2025 Sep 26:S2090-1232(25)00756-8. doi: 10.1016/j.jare.2025.09.053.
Yujie Yang 1 Yian Wang 1 Hongke Qu 1 Dan Wang 1 Junshang Ge 1 Pan Wu 1 Qijia Yan 2 Pan Chen 3 Bo Xiang 4 Ming Zhou 4 Can Guo 4 Wei Xiong 1 Lei Shi 5 Zhaoyang Zeng 6
Affiliations

Affiliations

  • 1 NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410000 Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410000 Hunan, China.
  • 2 Department of Pathology, Xiangya Hospital, Central South University, Changsha 410000 Hunan, China.
  • 3 NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410000 Hunan, China.
  • 4 Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410000 Hunan, China; Furong Laboratory, Changsha 410000 Hunan, China.
  • 5 Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410000 Hunan, China; Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha 410000 Hunan, China. Electronic address: shilei81@csu.edu.cn.
  • 6 NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410000 Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410000 Hunan, China; Furong Laboratory, Changsha 410000 Hunan, China. Electronic address: zengzhaoyang@csu.edu.cn.
Abstract

Introduction: CircRNAs play critical roles in the onset and progression of nasopharyngeal carcinoma (NPC), although their underlying mechanisms remain incompletely understood.

Objectives: In this study, we investigated the mechanism of circCDYL in promoting the proliferation, invasion and migration of NPC in vitro and in vivo.

Methods: We reanalyzed RNA Sequencing data (GSE137543, PRJNA391554) and validated findings with RT-qPCR and in situ hybridization experiments. Functional assays were subsequently performed both in vitro and in vivo.

Results: We identified circCDYL as being highly expressed in NPC, with its expression levels positively correlated with clinical tumor staging. Functionally, circCDYL promotes tumor proliferation and metastasis both in vitro and in vivo. Mechanistically, circCDYL binds to the 3'-UTR of LDHA mRNA, stabilizing it and upregulating LDHA protein expression, thereby enhancing cellular glycolysis and increasing lactate production and accumulation. The elevated lactate, in turn, promotes lactylation of the actin-binding protein CFL1 at lysine 22. This modification reduces cell adhesion and stiffness, ultimately facilitating tumor cell proliferation, invasion, and migration.

Conclusion: These findings indicate that circCDYL and its downstream pathways may serve as potential diagnostic markers or therapeutic targets for NPC.

Keywords

CFL1; Glycolysis; Lactylation; Nasopharyngeal carcinoma; circCDYL.

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