<scp>FOXM1</scp> Facilitates <scp>NSCLC</scp> Tumorigenesis Through the Transcriptional Regulation of <scp>UBE2C</scp>

Forkhead box M1 (FOXM1), a critical transcription factor, is implicated in tumorigenesis by regulating cell cycle progression, proliferation, and metastasis. Similarly, Ubiquitin-conjugating enzyme 2C (UBE2C), a key component of the ubiquitin-proteasome system, plays a pivotal role in mitotic progression and genomic stability. Aberrant overexpression of FOXM1 and UBE2C has been reported in various malignancies; however, their functional interplay in NSCLC remains poorly understood. In this study, we investigated the oncogenic roles of FOXM1 and UBE2C in NSCLC through in vitro and in vivo models, as well as clinical specimen analysis. Our findings demonstrate that FOXM1 transcriptionally upregulates UBE2C, thereby promoting NSCLC cell proliferation, invasion, and tumor progression via activation of oncogenic signaling pathways. Mechanistically, FAM64A stabilized FOXM1 expression, contributing to its pro-tumorigenic effects on NSCLC progression. Furthermore, FOXM1/UBE2C axis disruption impairs tumor growth, highlighting its potential as a novel therapeutic target. This study provides new insights into the molecular mechanisms underlying NSCLC pathogenesis and suggests that targeting the FAM64A/FOXM1/UBE2C axis may offer an effective strategy for NSCLC treatment.