ArticlePloS one2011
Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 2 of them syntheses that pooled it.
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Who cites it
121 citing papers in PubMed, 2 syntheses or guidelines pooled it, 216 citations in OpenAlex.
- The Impact of Stroma Admixture on Molecular Subtypes and Prognostic Gene Signatures in Serous Ovarian Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- Gene expression profiling of 1200 pancreatic ductal adenocarcinoma reveals novel subtypes.BMC cancer · 2018Pooled it
- Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (CDC25A) expression in cancer.The Journal of biological chemistry · 2012Trial
- Trial
- Characterizing intra- and intertumor heterogeneity in ovarian high-grade serous carcinoma subtypes using single-cell and spatial transcriptomics.Genome research · 2026Article
- Transcriptome signatures for the identification of bevacizumab responders in ovarian cancer.Genome medicine · 2026Article
- Impact of Anatomical Site on RNA-Based Molecular Subtypes in Paired High-Grade Serous Ovarian Carcinoma Samples.Cancers · 2026Article
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Exploring survival-associated transcriptomic subtypes in ovarian cancer using RNAseq from FFPE tissues in a clinical trial cohort.Translational oncology · 2026Article
- Dual regulation of PINK1/PARKIN-mediated mitochondrial autophagy in ovarian cancer progression and drug resistance: mechanisms and therapeutic potentials.Journal of ovarian research · 2026Review
- Targeting the Lin28/let-7 Axis with Compounds to Regulate Transcriptional Control in Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
- Claudins in ovarian cancer: emerging biomarkers and therapeutic targets.Tissue barriers · 2026Review
- Multimodal AI in high-grade serous ovarian cancer: integrated prediction and clinical decision-making.Frontiers in oncology · 2026Review
- Inhibition of RNA-binding proteins enhances immunotherapy in ovarian cancer.Signal transduction and targeted therapy · 2025Article
- Tumour-infiltrating leucocytes as prognostic biomarkers of bevacizumab-treated ovarian cancer patients results from the phase IV MITO16A/MaNGO OV-2 clinical trial.NPJ precision oncology · 2025Article
- Characterizing intra- and inter-tumor heterogeneity in Ovarian high-grade serous carcinoma subtypes using single-cell and spatial transcriptomics.bioRxiv : the preprint server for biology · 2025Article
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- OVsignGenes: A Gene Expression-Based Neural Network Model Estimated Molecular Subtype of High-Grade Serous Ovarian Carcinoma.Cancers · 2024Article
- ClassifieR 2.0: expanding interactive gene expression-based stratification to prostate and high-grade serous ovarian cancer.BMC bioinformatics · 2024Article
- Molecular Subtypes of High-Grade Serous Ovarian Cancer across Racial Groups and Gene Expression Platforms.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular subtypes of serous ovarian cancer have been recently described. Using data from independent datasets including over 900 primary tumour samples, we show that deregulation of the Let-7 pathway is specifically associated with the C5 molecular subtype of serous ovarian cancer. DNA copy number and gene expression of HMGA2, alleles of Let-7, LIN28, LIN28B, MYC, MYCN, DICER1, and RNASEN were measured using microarray and quantitative reverse transcriptase PCR. Immunohistochemistry was performed on 127 samples using tissue microarrays and anti-HMGA2 antibodies. Fluorescence in situ hybridisation of bacterial artificial chromosomes hybridized to 239 ovarian tumours was used to measure translocation at the LIN28B locus. Short interfering RNA knockdown in ovarian cell lines was used to test the functionality of associations observed. Four molecular subtypes (C1, C2, C4, C5) of high-grade serous ovarian cancers were robustly represented in each dataset and showed similar pattern of patient survival. We found highly specific activation of a pathway involving MYCN, LIN28B, Let-7 and HMGA2 in the C5 molecular subtype defined by MYCN amplification and over-expression, over-expression of MYCN targets including the Let-7 repressor LIN28B, loss of Let-7 expression and HMGA2 amplification and over-expression. DICER1, a known Let-7 target, and RNASEN were over-expressed in C5 tumours. We saw no evidence of translocation at the LIN28B locus in C5 tumours. The reported interaction between LIN28B and Let-7 was recapitulated by siRNA knockdown in ovarian cancer cell lines. Our results associate deregulation of MYCN and downstream targets, including Let-7 and oncofetal genes, with serous ovarian cancer. We define for the first time how elements of an oncogenic pathway, involving multiple genes that contribute to stem cell renewal, is specifically altered in a molecular subtype of serous ovarian cancer. By defining the drivers of a molecular subtype of serous ovarian cancers we provide a novel strategy for targeted therapeutic intervention.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.