CircCDYL promotes glycolysis to drive the progression of nasopharyngeal carcinoma

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.