Mechanistic insights into 5-HT-induced non-small cell lung cancer metastasis through the SNRPG/WT1/CDK14 Axis

Non-small cell lung cancer (NSCLC) is a leading malignant tumor with high mortality. Reliable biomarkers for prognosis are lacking, leading to poor outcomes in metastatic NSCLC. This study investigates the 5-hydroxytryptamine (5-HT)/small nuclear ribonucleoprotein polypeptide G (SNRPG) axis in NSCLC metastasis, exploring molecular mechanisms and clinical relevance. Firstly, gut microbiota metabolomic analysis revealed significant enrichment of L-tryptophan (Trp) and serotonin pathways in NSCLC metastasis. Functionally, 5-HT positively regulated in-vivo and in-vitro NSCLC cells' malignant phenotype through the SNRPG. Rescue experiments showed that overexpressing SNRPG partially reversed the 5-HT- promoting effect on ESCC cells' migration and invasion ability. Further RNA-seq identified cyclin-dependent kinase 14 (CDK14) downstream of SNRPG. Mechanistically, SNRPG suppressed CDK14 expression by regulating WT1 activity, inhibiting the migration and invasion of NCLC cells. Our study demonstrated the 5-HT/SNRPG/WT1/CDK14 axis significantly impacts NSCLC metastasis, presenting 5-HT/SNRPG as a potential therapeutic target for NSCLC patients.