SLC35F2 promotes the progression of NSCLC via regulating CREB1 expression.

Abstract

SLC35F2 has emerged as a potential oncogenic driver in non-small cell lung cancer (NSCLC), yet its mechanistic role in tumor progression remains poorly understood. This study aimed to explore the mechanism of SLC35F2 in mediating non-small cell lung cancer (NSCLC) progression through the cAMP signaling pathway. By analyzing TCGA and GEPIA databases, the present research found that SLC35F2 expression was significantly elevated in NSCLC tissues compared to normal lung tissues, with high SLC35F2 levels correlating with poor patient prognosis (P < 0.05). Functional enrichment analysis using R language revealed significant alterations in multiple pathways, including cAMP signaling, in SLC35F2-high NSCLC. Experimental validation through RT-qPCR and Western blot confirmed upregulated SLC35F2 expression in NSCLC cell lines. Knockdown of SLC35F2 inhibited cell proliferation, migration, and invasion while promoting apoptosis (P < 0.05), as demonstrated by CCK-8, EdU, colony formation, flow cytometry, TUNEL, scratch, and Transwell assays. Mechanistically, SLC35F2 suppression activated the cAMP signaling pathway, particularly through upregulation of the transcription factor CREB1. These findings suggest that SLC35F2 drives NSCLC progression by modulating the cAMP/CREB1 axis, highlighting its potential as a therapeutic target.