CircTAF15 (hsa_circ_0043138) promotes NSCLC progression through stabilizing YBX1 to initiate GOT1 transcription.

Non-small cell lung cancer (NSCLC) remains one of the most lethal malignancies globally, largely due to its asymptomatic early course and poor prognosis at advanced stages. The rapid proliferation of NSCLC cells drives an increased demand for bioenergy and biosynthetic precursors, which is met through metabolic reprogramming. Targeting this reprogramming to cut off the energy for tumors therefore represents a promising therapeutic strategy for NSCLC. We analyzed two NSCLC circRNA microarray datasets (GSE146689 and GSE158695) to identify a novel circRNA, which was confirmed through Sanger sequencing as being derived from exons 3-6 of the TAF15 pre-mRNA, designated circTAF15. We performed knockdown experiments to investigate the functional role of circTAF15 in NSCLC cells. From a mechanistic perspective, we assessed the interaction between circTAF15 and YBX1, investigating the inhibitory role of circTAF15 in ubiquitin-mediated degradation. Furthermore, we analyzed the influence of the circTAF15-YBX1 complex on the transcriptional activation of the key enzyme in glutamine metabolism, GOT1. We identified a novel circRNA, circTAF15, confirmed by Sanger sequencing to originate from exons 3-6 of the TAF15 pre-mRNA. Knockdown of circTAF15 significantly suppressed NSCLC cell proliferation and migration by inhibiting glutamine metabolism. Mechanistically, circTAF15 binds to YBX1, protecting it from ubiquitination-mediated degradation. This circTAF15-YBX1 complex enhances the transcriptional activation of GOT1, a key enzyme in glutamine metabolism, thereby facilitating NSCLC cell proliferation and migration. Our findings reveal a critical circRNA-driven regulatory axis in NSCLC metabolism and highlight circTAF15 as a promising therapeutic target.