Abstract

Background Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality with limited treatment efficacy. Small nucleolar RNAs (snoRNAs) have emerged as potential key players in tumorigenesis, but their roles in NSCLC are largely unexplored. Our previous study identified SCARNA20 as significantly downregulated in NSCLC tissues, suggesting a potential tumor-suppressive function. Thus, in order to further explore the role of SCARNA20 in NSCLC, we conducted this study to verify its function. Methods The biological functions of SCARNA20 were investigated in vitro using NSCLC cell lines (A549, H1299, H1437). Experiments included Cell Counting Kit-8 (CCK-8) and colony formation assays for proliferation, flow cytometry for apoptosis and cell cycle analysis, and Transwell and wound healing assays for migration and invasion. A subcutaneous xenograft mouse model was established using A549 cells overexpressing SCARNA20 to assess its impact on tumor growth in vivo . Tumor tissues were analyzed via hematoxylin and eosin (H&E) and immunohistochemical staining (Ki-67, Caspase-3). Transcriptome sequencing and bioinformatics analysis were performed to explore underlying mechanisms. Results Overexpression of SCARNA20 significantly inhibited NSCLC cell proliferation, colony formation, migration, and invasion in vitro . It also promoted cell apoptosis and induced cell cycle arrest, primarily at the G0/G1 phase. In the mouse xenograft model, SCARNA20 overexpression markedly suppressed tumor growth, reduced tumor weight, decreased Ki-67 expression (proliferation marker), and increased Caspase-3 expression (apoptosis marker). Transcriptome analysis revealed 2604 differentially expressed genes following SCARNA20 overexpression, which were enriched in pathways such as cytokine-cytokine receptor interaction, MAPK signaling, and TNF signaling. Conclusions SCARNA20 acts as a tumor suppressor in NSCLC, inhibiting malignant phenotypes including cell proliferation, migra