TFAP2A-Induced Upregulation of LncRNA NUTM2A-AS1 Promotes LUAD Progression Through a miR-409-5p/SLC35F2 Regulatory...

Long non-coding RNAs (LncRNAs) play pivotal roles in lung adenocarcinoma (LUAD) progression. However, the upstream transcriptional regulation and downstream mechanisms of LncRNA NUTM2A-AS1 in LUAD remain largely unexplored. The expression levels of NUTM2A-AS1, TFAP2A, miR-409-5p and SLC35F2 in LUAD tissues and cell lines were analysed using public databases and qRT-PCR. The biological functions of this axis in LUAD cells were evaluated through CCK-8, Transwell and apoptosis assays. The molecular interactions among TFAP2A, NUTM2A-AS1, miR-409-5p and SLC35F2 were validated via chromatin immunoprecipitation (ChIP), dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Both NUTM2A-AS1 and TFAP2A were significantly upregulated in LUAD and correlated with poor prognosis. Mechanistically, the transcription factor TFAP2A directly bound to the NUTM2A-AS1 promoter to activate its transcription. Functionally, NUTM2A-AS1 promoted LUAD cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), while suppressing apoptosis. Furthermore, NUTM2A-AS1 may function as a competing endogenous RNA-like regulator by interacting with miR-409-5p, thereby upregulating the expression of the solute carrier family member SLC35F2. Rescue assays demonstrated that SLC35F2 knockdown attenuated the oncogenic phenotypes induced by TFAP2A or NUTM2A-AS1, while miR-409-5p restoration suppressed SLC35F2 expression and cell-cycle progression. Our study supports a TFAP2A/NUTM2A-AS1/miR-409-5p/SLC35F2 regulatory model that contributes to LUAD progression. These findings suggest that the TFAP2A/NUTM2A-AS1/miR-409-5p/SLC35F2 axis contributes to LUAD progression and may provide potential biomarkers and therapeutic targets.