ArticleOncogene2017
let-7b and let-7c microRNAs promote histone H2B ubiquitylation and inhibit cell migration by targeting multiple components of the H2B deubiquitylation machinery.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- MicroRNA Expression Links Transportation Environmental Burden to Late-Stage Triple-Negative Breast Cancer.Genes · 2026Article
- E3 ubiquitin ligase RNF40: Structure, function and its context‑dependent roles in tumorigenesis (Review).Oncology reports · 2026Review
- TAZ facilitates breast tumor growth by promoting an immune-suppressive tumor microenvironment.Molecular oncology · 2023Article
- Anwuligan inhibits the progression of non-small cell lung cancer via let-7c-3p/PI3K/AKT/mTOR axis.Cancer medicine · 2023Article
- Influence of the Mediterranean Diet on Healthy Aging.International journal of molecular sciences · 2023Review
- Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN.International journal of oral science · 2022Article
- Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis.International journal of molecular sciences · 2022Review
- The significance of the crosstalk between ubiquitination or deubiquitination and ncRNAs in non-small cell lung cancer.Frontiers in oncology · 2022Review
- Mediterranean diet and the hallmarks of ageing.European journal of clinical nutrition · 2021Review
- Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value.Frontiers in oncology · 2021Review
- Frontiers of MicroRNA Signature in Non-small Cell Lung Cancer.Frontiers in cell and developmental biology · 2021Review
- A Division of Labor between YAP and TAZ in Non-Small Cell Lung Cancer.Cancer research · 2020Article
- Epigenetic regulation of the Warburg effect by H2B monoubiquitination.Cell death and differentiation · 2020Article
- CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis.BMC medical genomics · 2019Article
- Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer.Clinical and translational medicine · 2019Review
- Role of RNF20 in cancer development and progression - a comprehensive review.Bioscience reports · 2018Review
- Morphoregulatory functions of the RNA-binding motif protein 3 in cell spreading, polarity and migration.Scientific reports · 2018Article
- Emerging roles of microRNAs in cancer.Current opinion in genetics & development · 2018Review
- Deubiquitinating Enzymes and Bone Remodeling.Stem cells international · 2018Review
- Liver kinase B1 restoration promotes exosome secretion and motility of lung cancer cells.Oncology reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Monoubiquitylation of histone H2B (H2Bub1) is catalyzed mainly by the RNF20/RNF40 complex and erased by multiple deubiquitylating enzymes (DUBs). H2Bub1 influences many aspects of chromatin function, including transcription regulation and DNA repair. Cancer cells often display reduced levels of H2Bub1, and this reduction may contribute to cancer progression. The let-7 family of microRNAs (miRNAs) comprises multiple members with reported tumor-suppressive features, whose expression is frequently downregulated in cancer. We now report that let-7b and let-7c can positively regulate cellular H2Bub1 levels. Overexpression of let-7b and let-7c in a variety of non-transformed and cancer-derived cell lines results in H2Bub1 elevation. The positive effect of let-7b and let-7c on H2Bub1 levels is achieved through targeting of multiple mRNAs, coding for distinct components of the H2B deubiquitylation machinery. Specifically, let-7b and let-7c bind directly and inhibit the mRNAs encoding the DUBs USP42 and USP44, and also the mRNA encoding the adapter protein ATXN7L3, which is part of the DUB module of the SAGA complex. RNF20 knockdown (KD) strongly reduces H2Bub1 levels and increases the migration of non-transformed mammary epithelial cells and breast cancer-derived cells. Remarkably, overexpression of let-7b, which partly counteracts the effect of RNF20 KD on H2Bub1 levels, also reverses the pro-migratory effect of RNF20 KD. Likewise, ATXN7L3 KD also increases H2Bub1 levels and reduces cell migration, and this anti-migratory effect is abolished by simultaneous KD of RNF20. Together, our findings uncover a novel function of let-7 miRNAs as regulators of H2B ubiquitylation, suggesting an additional mechanism whereby these miRNAs can exert their tumor-suppressive effects.
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