Decoding the tumor-suppressive mechanisms of NDRG family genes in colon cancer

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-07-19 DOI:10.1016/j.genrep.2025.102295

Xia Weng , Jiyun Zhu , Xiaoshuai Zhou

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引用次数: 0

Abstract

Background

The NDRG family regulates biological processes in various cancers, but its mechanistic role in colon adenocarcinoma (COAD) remains unclear.

Methods

Through multi-omics analysis, we evaluated the expression profiles of NDRG family members across pan-cancer and COAD contexts, including genomic correlations (TMB, MSI), clinical prognosis, protein interactions, and immune infiltration. Key tumor-suppressive functions and downstream pathways were validated via in vitro experiments.

Results

NDRG family genes were generally downregulated in tumors, showing negative correlations with TMB and MSI (P < 0.05), indicative of tumor-suppressive roles. Notably, NDRG4 was significantly downregulated in COAD and positively correlated with T/B cell subtypes and dendritic cell infiltration (r = 0.32–0.45). Functional experiments demonstrated that NDRG4 overexpression suppressed tumor growth and metastasis by inhibiting nitrogen metabolism pathways (KEGG enrichment P = 1.2 × 10⁻⁵). Synergistic inhibition of PBK enhanced antitumor efficacy (68 % reduction in proliferation).

Conclusion

This study provides the first comprehensive elucidation of the tumor-suppressive and immune-modulatory roles of the NDRG family (particularly NDRG4) in COAD, identifying NDRG4 as a potential therapeutic target and prognostic biomarker.

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破解结肠癌NDRG家族基因的肿瘤抑制机制

NDRG家族调控多种癌症的生物学过程，但其在结肠腺癌（COAD）中的机制作用尚不清楚。方法通过多组学分析，我们评估了NDRG家族成员在泛癌症和COAD背景下的表达谱，包括基因组相关性（TMB、MSI）、临床预后、蛋白质相互作用和免疫浸润。通过体外实验验证了关键的肿瘤抑制功能和下游途径。结果sndrg家族基因在肿瘤中普遍下调，与TMB、MSI呈负相关(P <；0.05)，提示肿瘤抑制作用。值得注意的是，NDRG4在COAD中显著下调，并与T/B细胞亚型和树突状细胞浸润呈正相关（r = 0.32-0.45）。功能实验表明，NDRG4过表达通过抑制氮代谢途径抑制肿瘤生长和转移（KEGG富集P = 1.2 × 10−5）。协同抑制PBK增强抗肿瘤疗效（减少68%的增殖）。结论本研究首次全面阐明了NDRG家族（特别是NDRG4）在COAD中的肿瘤抑制和免疫调节作用，确定了NDRG4作为潜在的治疗靶点和预后生物标志物。

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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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.