NDUFA10: An Emerging Oncogenic Driver of Metastasis in LungAdenocarcinoma

INTRODUCTION: mRNA sequencing analysis suggested that ubiquinone oxidoreductase subunit A10 (NDUFA10) may function as a key downstream effector of circRAPGEF5 in lung adenocarcinoma (LUAD) progression; however, the underlying mechanism remains unclear. This study aimed to explore the expression and clinical significance of NDUFA10 in LUAD cells and its role in cell proliferation and metastasis. METHODS: Variations in NDUFA10 mRNA and protein expression between LUAD and adjacent normal tissues were assessed using the Cancer Genome Atlas Program (TCGA) and Tumor Immune Estimation Resource (TIMER) databases. These findings were subsequently validated in LUAD cell lines via Reverse Transcription Quantitative PCR (RT-qPCR). Further analyses included clinical correlation, Receiver Operating Characteristic (ROC), survival analysis, and Gene Set Enrichment Analysis (GSEA) of NDUFA10. The functional role of NDUFA10 was investigated in vitro at the cellular level. RESULTS: NDUFA10 mRNA expression was significantly upregulated in pan-cancer analyses and specifically in LUAD. Its expression levels correlated with clinical parameters, including metastasis (M stage) and patient gender. Elevated NDUFA10 expression demonstrated a negative correlation with overall survival (OS) and first progression (FP), and was associated with the best efficacy of anti-PD-1/PD-L1 antibody therapies. GSEA indicated significant enrichment of NDUFA10-related genes in pathways involving WNT and Notch signaling, as well as the TGFβ pathway regulating the epithelial-mesenchymal transition (EMT). In vitro, knockdown of NDUFA10 significantly suppressed LUAD cell proliferation, colony formation, migration, and invasion compared to control cells. DISCUSSION: This study focuses on the role of NDUFA10 in lung adenocarcinoma (LUAD). Through database screening and experimental verification, it was found that NDUFA10 is upregulated in LUAD. Its high expression is associated with advanced N stage (N2/N3), high pathological stage (III/IV), poor therapeutic effect and advanced age, suggesting its potential as a biomarker for poor diagnosis and prognosis. Further analysis indicates that NDUFA10 is associated with immune infiltration and involves pathways such as neuroactive ligand-receptor interaction and chemokine signaling. In vitro experiments have confirmed that knocking down NDUFA10 can inhibit the proliferation and metastasis of lung adenocarcinoma cells. This study provides a preliminary basis for the function and mechanism of NDUFA10 in LUAD. In the future, we will further explore how it affects tumor progression through the WNT/Notch/TGFβ pathway or ROS/ energy metabolism. CONCLUSION: Silencing NDUFA10 suppresses LUAD cell proliferation, migration, and invasion. The study suggested that circRAPGEF5 regulated NDUFA10 to facilitate the progression of LUAD.