NOC4L serves as a novel prognostic marker and therapeutic target for lung adenocarcinoma

Nucleolus complex-associated 4 homologue (NOC4L), a ribosome biogenesis factor essential for small subunit processome assembly, has demonstrated oncogenic potential across multiple malignancies. Nevertheless, the mechanistic contributions of NOC4L to lung adenocarcinoma (LUAD) pathogenesis remain poorly characterized. This study systematically investigates the expression, clinical relevance, and molecular functions of NOC4L in LUAD. We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) LUAD cohort and normal lung tissues from the Genotype-Tissue Expression (GTEx) project to quantify tumor-specific NOC4L expression. Functional enrichment analysis employing Gene Ontology and KEGG pathways revealed associations with ribosome biogenesis, cell cycle regulation, and transcriptional dysregulation. Single-cell RNA analysis were interrogated to identify cellular subpopulations with elevated NOC4L expression. Immune microenvironment alterations were evaluated using ssGSEA algorithms, while methylation aberrations were mapped via MethSurv. The STarBase database and prognostic model were utilized to construct competing endogenous RNA (ceRNA) networks regulating NOC4L. siRNA mediated NOC4L knockdown in A549 and H1299 LUAD cell lines was performed to assess phenotypic impacts through CCK-8 proliferation assays, colony formation analyses, and migration experiments. NOC4L exhibited significant overexpression in LUAD compared to normal tissues (P<0.001), correlating with advanced TNM staging. Enrichment analysis indicated that NOC4L is associated with key pathways involved in cancer development. Single-cell analysis localized NOC4L overexpression predominantly within fibroblast subpopulations (c-9 cluster). High NOC4L expression correlated with immune microenvironment disorders, abnormal methylation levels, and mutations. Mechanistic studies identified the SNHG1/LINC00662-miR-101-3p axis as the predominant ceRNA regulator of NOC4L. Functional silencing of NOC4L significantly inhibited the proliferation, clone formation, and migration abilities of LUAD cells. NOC4L as an oncogenic protein promotes the cancer progression related to immune infiltrates, which underscores that NOC4L is a promising diagnostic and prognostic marker that may facilitate targeted therapies in LUAD.