Journal of advanced research · 2025
CircCDYL promotes glycolysis to drive the progression of nasopharyngeal carcinoma.
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Yang Yujie, Wang Yian, Qu Hongke, Wang Dan, Ge Junshang, Wu Pan, Yan Qijia, Chen Pan, Xiang Bo, Zhou Ming, Guo Can, Xiong Wei, Shi Lei, Zeng Zhaoyang
Аннотация
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.
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.