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

Mingming Wang , Yang Lv , Zhenyu Wang , Richard Mprah , Yinchuan Ding , Cui Li , Min Xue
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
no4l可作为肺腺癌新的预后标志物和治疗靶点
核核体复合体相关4同源物(NOC4L)是小亚基过程体组装所必需的核糖体生物发生因子,已被证明在多种恶性肿瘤中具有致癌潜力。尽管如此,nocl在肺腺癌(LUAD)发病机制中的作用仍不清楚。本研究系统探讨了no4l在LUAD中的表达、临床意义及分子功能。方法分析来自癌症基因组图谱(TCGA) LUAD队列的RNA测序数据和来自基因型-组织表达(GTEx)项目的正常肺组织的RNA测序数据,量化肿瘤特异性NOC4L的表达。利用Gene Ontology和KEGG途径进行的功能富集分析揭示了与核糖体生物发生、细胞周期调节和转录失调的关联。通过单细胞RNA分析,鉴定出no4l表达升高的细胞亚群。使用ssGSEA算法评估免疫微环境改变,同时通过MethSurv绘制甲基化畸变图。利用STarBase数据库和预后模型构建调控NOC4L的竞争性内源性RNA (ceRNA)网络。在A549和H1299 LUAD细胞系中进行siRNA介导的NOC4L敲低,通过CCK-8增殖实验、菌落形成分析和迁移实验来评估表型影响。结果与正常组织相比,not4l在LUAD中表现出显著的过表达(P < 0.001),与TNM晚期分期相关。富集分析表明,NOC4L与参与癌症发展的关键途径相关。单细胞分析表明,NOC4L主要在成纤维细胞亚群(c-9簇)中过表达。高表达的NOC4L与免疫微环境紊乱、甲基化水平异常和突变相关。机制研究发现SNHG1/LINC00662-miR-101-3p轴是NOC4L的主要ceRNA调节因子。功能性沉默no4l可显著抑制LUAD细胞的增殖、克隆形成和迁移能力。结论NOC4L作为一种致癌蛋白,可促进与免疫浸润相关的肿瘤进展,提示NOC4L是一种有前景的LUAD诊断和预后标志物,可能促进靶向治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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