NOL10

Overview

NOL10 (Nucleolar Protein 10) is a nucleolar protein whose expression is regulated by a germline risk SNP (rs4519489) at 2p25 via enhanced binding of the transcription factor USF1. NOL10 is overexpressed in prostate adenocarcinoma (PRAD) relative to normal tissue and functions as an oncogene driving cell-cycle progression through E2F target and G2M checkpoint gene networks. It was identified as the functional effector of a prostate cancer GWAS risk locus.

Alterations observed in the corpus

  • eQTL target of rs4519489 at 2p25: the intronic risk A allele drives higher NOL10 mRNA via enhanced USF1 binding; overexpressed in PRAD tumors vs. normals across multiple cohorts; high expression correlates with stage, lymph-node metastasis, Gleason score, biochemical recurrence (BCR), and shorter OS. Knockdown abrogates proliferation, colony formation, migration, invasion, EMT, and xenograft growth; overexpression promotes them. Acts via cell-cycle regulators (E2F targets, G2M checkpoint: DLGAP5, MCM4, KIF20B, DIAPH3, SUV39H1, CENPE, GINS2, HMGB3, CDC6) PMID:28927585.

Cancer types (linked)

  • Prostate adenocarcinoma (PRAD): overexpressed in tumor vs. normal; high expression associated with advanced stage, lymph-node metastasis, Gleason score, BCR, and shorter OS; rs4519489 A/A genotype is an independent OS predictor (Cox HR=13.05, 95% CI 1.16–147.20, P=0.038); NOL10 cell-cycle signature is an independent BCR-free-survival predictor in CPGEA (HR=2.86, P=0.010), with fixed-effects meta-analysis HR=2.49 across CPGEA / MSKCC / TCGA / DKFZ PMID:28927585.

Co-occurrence and mutual exclusivity

  • Highly co-expressed with USF1, its upstream transcriptional activator, across multiple prostate cancer cohorts; co-expression of NOL10 + USF1 outperforms either marker alone in time-dependent ROC analysis for 1–10 year survival PMID:28927585.
  • APOBEC mutational signature (APOBEC3A/APOBEC3B) modestly enriched at the NOL10 locus in CPGEA and TCGA PRAD, suggesting ectopic APOBEC mutagenesis as a complementary somatic contributor to NOL10 deregulation PMID:28927585.

Therapeutic relevance

  • The rs4519489-USF1-NOL10 axis is proposed as a candidate therapeutic target; degrading USF1 or NOL10 could blunt cell-cycle (E2F / G2M) drive in A-allele-carrying tumors. No clinical drug or trial is reported; this is a preclinical hypothesis only PMID:28927585.

Open questions

  • Clinical translation of USF1/NOL10 inhibition remains entirely preclinical; no validated small-molecule inhibitor of NOL10 is described.
  • Generalizability beyond PRAD to other cancer types has not been evaluated.

Sources

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