ArticlePloS one2012
Hiwi mediated tumorigenesis is associated with DNA hypermethylation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- PIWI family proteins as prognostic markers in cancer: a systematic review and meta-analysis.Cellular and molecular life sciences : CMLS · 2020Pooled it
- The Chromaverse Is Colored by Triplexes Formed Through the Interactions of Noncoding RNAs with HNPRNPU, TP53, AGO, REL Proteins, Intrinsically-Disordered Regions, and Flipons.International journal of molecular sciences · 2026Article
- Biological roles and clinical potential of piRNAs in cancer: Insights into glioblastoma.Iranian journal of basic medical sciences · 2026Review
- Mechanisms Behind the Impact of PIWI Proteins on Cancer Cells: Literature Review.International journal of molecular sciences · 2024Review
- PIWIL1 is recruited to centrosomes during mitosis in colorectal cancer cells and is linked to cell cycle progression.Scientific reports · 2024Article
- Transfer RNA‑derived small RNAs: A class of potential biomarkers in multiple cancers (Review).Oncology letters · 2024Review
- HPV16 E6/E7-mediated regulation of PiwiL1 expression induces tumorigenesis in cervical cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Downregulation of transposable elements extends lifespan in Caenorhabditis elegans.Nature communications · 2023Article
- Epigenetic roles of PIWI proteins and piRNAs in colorectal cancer.Cancer cell international · 2021Review
- MRI detection of the malignant transformation of stem cells through reporter gene expression driven by a tumor-specific promoter.Stem cell research & therapy · 2021Article
- Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression.Cell reports · 2021Article
- Elevated P-Element-Induced Wimpy-Testis-Like Protein 1 Expression Predicts Unfavorable Prognosis for Patients with Various Cancers.Journal of oncology · 2021Review
- Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications.Frontiers in cell and developmental biology · 2021Review
- PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer.Cancers · 2020Article
- The Clinical Significance of PIWIL3 and PIWIL4 Expression in Pancreatic Cancer.Journal of clinical medicine · 2020Article
- Molecular and Functional Characterization of the Somatic PIWIL1/piRNA Pathway in Colorectal Cancer Cells.Cells · 2019Article
- Piwi-like 1 protein expression is a prognostic factor for renal cell carcinoma patients.Scientific reports · 2019Article
- Article
- Piwi-like 1 and -2 protein expression levels are prognostic factors for muscle invasive urothelial bladder cancer patients.Scientific reports · 2018Article
- Hiwi overexpression does not affect proliferation, migration or apoptosis of liver cancer cellsOncology letters · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression of Piwi proteins is confined to early development and stem cells during which they suppress transposon migration via DNA methylation to ensure genomic stability. Piwi's genomic protective function conflicts with reports that its human ortholog, Hiwi, is expressed in numerous cancers and prognosticates shorter survival. However, the role of Hiwi in tumorigenesis has not been examined. Here we demonstrate that (1) over-expressing Hiwi in sarcoma precursors inhibits their differentiation in vitro and generates sarcomas in vivo; (2) transgenic mice expressing Hiwi (mesodermally restricted) develop sarcomas; and (3) inducible down-regulation of Hiwi in human sarcomas inhibits growth and re-establishes differentiation. Our data indicates that Hiwi is directly tumorigenic and Hiwi-expressing cancers may be addicted to Hiwi expression. We further show that Hiwi associated DNA methylation and cyclin-dependent kinase inhibitor (CDKI) silencing is reversible along with Hiwi-induced tumorigenesis, via DNA-methyltransferase inhibitors. Our studies reveal for the first time not only a novel oncogenic role for Hiwi as a driver of tumorigenesis, but also suggest that the use of epigenetic agents may be clinically beneficial for treatment of tumors that express Hiwi. Additionally, our data showing that Hiwi-associated DNA hyper-methylation with subsequent genetic and epigenetic changes favoring a tumorigenic state reconciles the conundrum of how Hiwi may act appropriately to promote genomic integrity during early development (via transposon silencing) and inappropriately in adult tissues with subsequent tumorigenesis.
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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.