Affinage

PIWIL1

Piwi-like protein 1 · UniProt Q96J94

Length
861 aa
Mass
98.6 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIWIL1 is a PIWI-clade Argonaute protein that functions as a piRNA-guided endonuclease essential for transposon silencing and gametogenesis in both sexes. Its MID domain specifies 5′-uridine recognition of piRNAs, while the PIWI domain — potentiated by the auxiliary factor GTSF1 — cleaves complementary transcripts with relaxed mismatch tolerance, enabling silencing of rapidly diverging transposable elements (PMID:24757166, PMID:35772669, PMID:37344600). PIWIL1 undergoes PRMT5-mediated symmetrical dimethylarginine modification that recruits Tudor-domain proteins, and interacts with TDRD2 through a methylation-independent mechanism to facilitate piRNA 3′-end trimming; during late spermiogenesis, piRNA-loaded PIWIL1 switches from translational activation to mRNA degradation before being eliminated by APC/C-mediated ubiquitination (PMID:20360382, PMID:29118143, PMID:35403682). When ectopically expressed in cancers lacking piRNAs, PIWIL1 acts as a piRNA-independent co-activator of APC/C to promote metastasis, and drives DNA hypermethylation through DNMT1 upregulation (PMID:32203416, PMID:22438986).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 Medium

    Establishing that PIWIL1 is a germline-restricted PIWI-family protein expressed in human spermatocytes and round spermatids resolved where this Argonaute functions during normal development.

    Evidence RT-PCR, immunohistochemistry, and chromosomal mapping in human testis

    PMID:12037681

    Open questions at the time
    • No functional assay; expression pattern alone does not define mechanism
    • Female germline expression not examined
  2. 2010 Medium

    Demonstrating that PRMT5 installs symmetrical dimethylarginines on PIWIL1 that recruit Tudor-domain proteins revealed how post-translational modification organizes the piRNA pathway protein machinery.

    Evidence Biochemical characterization and protein interaction studies

    PMID:20360382

    Open questions at the time
    • Specific Tudor-domain partners for mammalian PIWIL1 not fully enumerated
    • Functional consequence of blocking sDMA on PIWIL1 in vivo not shown in this study
  3. 2012 Medium

    Showing that PIWIL1 overexpression induces DNA hypermethylation, silences CDK inhibitors, and generates sarcomas in transgenic mice — reversed by DNMT inhibitors — established a causal oncogenic mechanism through epigenetic reprogramming.

    Evidence Transgenic mouse model, overexpression/knockdown in cell lines, DNA methylation analysis, DNMT inhibitor rescue

    PMID:22438986

    Open questions at the time
    • Direct PIWIL1–DNMT interaction not demonstrated
    • Whether piRNAs are present in these sarcoma models is unclear
  4. 2014 High

    Crystal structure of the MID domain and domain-swap experiments revealed how the MID-PIWI module specifies 5′-uridine recognition and strand orientation of bound piRNAs, explaining the biochemical basis of piRNA selection.

    Evidence Crystal structure, docking, mutational analysis, domain-swapping, in vivo piRNA biogenesis assays

    PMID:24757166

    Open questions at the time
    • Full-length mammalian PIWIL1 structure not yet solved at the time
    • How MID-PIWI cooperates with PAZ domain during loading was unresolved
  5. 2015 Medium

    Multiple studies expanded PIWIL1 biology beyond germ cells: it regulates cortical neuron migration via microtubule-associated proteins, binds and stabilizes Stathmin1 to suppress microtubule polymerization, and drives PTEN silencing through a DNMT1-mediated methylation axis in cancer.

    Evidence In utero electroporation knockdown in cortical neurons; Co-IP/ubiquitination/phosphorylation assays for Stathmin1 interaction; siRNA knockdown and bisulfite sequencing for DNMT1–PTEN axis

    PMID:26056945 PMID:26104391 PMID:26317901

    Open questions at the time
    • Neuron migration phenotype not tested in Piwil1 knockout mice
    • Stathmin1 interaction demonstrated in cancer cell lines — physiological relevance in germ cells unknown
    • Whether piRNAs participate in these non-germline contexts is not resolved
  6. 2017 High

    Crystal structure of TDRD2 bound to an unmethylated PIWIL1 peptide demonstrated a methylation-independent Tudor–PIWI interaction required for piRNA 3′-end trimming, distinguishing this from the sDMA-dependent Tudor interactions.

    Evidence Crystal structure, structural mutagenesis, in vitro piRNA trimming assay

    PMID:29118143

    Open questions at the time
    • In vivo validation in mammalian germ cells not performed
    • Identity of the 3′-end trimming nuclease acting downstream was not defined
  7. 2019 Medium

    UHRF1 was linked to the PIWI/PRMT5 axis during spermatogenesis, and behavioral studies revealed PIWIL1 knockdown in adult hippocampus enhances fear memory — broadening the functional contexts for PIWIL1 beyond reproduction.

    Evidence Conditional UHRF1 knockout mouse with DNA methylation and retrotransposon analysis; viral-mediated PIWIL1 knockdown with fear conditioning in adult mice

    PMID:30965112 PMID:31624244

    Open questions at the time
    • UHRF1–PIWIL1 physical interaction not directly shown
    • Behavioral phenotype mechanism (piRNA-dependent vs independent) not determined
    • Molecular targets of PIWIL1 in hippocampal neurons not identified
  8. 2020 High

    A pivotal study revealed that piRNAs act as a molecular switch: piRNA-loaded PIWIL1 is an APC/C substrate during spermiogenesis, but piRNA-free PIWIL1 in cancer becomes an APC/C co-activator targeting Pinin for degradation to drive metastasis — the first piRNA-independent enzymatic function for a PIWI protein.

    Evidence Co-IP, ubiquitination assays, mass spectrometry, in vivo tumor metastasis assays in pancreatic cancer

    PMID:32203416

    Open questions at the time
    • Whether other cancers use the same piRNA-independent APC/C co-activation is untested
    • Structural basis for piRNA-dependent vs -independent APC/C interaction modes unknown
  9. 2020 High

    The crystal structure of Drosophila Piwi–piRNA complex showed a non-canonical DVDK catalytic tetrad explaining loss of slicer activity, while restoration of DEDH conferred cleavage — establishing that nuclear PIWI evolved away from slicing toward co-transcriptional silencing.

    Evidence Cryo-crystallography at 2.9 Å, active-site mutagenesis, RNA cleavage assays

    PMID:32051406

    Open questions at the time
    • Applies to Drosophila nuclear Piwi; mammalian PIWIL1 retains slicer activity, so direct transferability is limited
    • How target dwell-time is regulated for co-transcriptional silencing remains unclear
  10. 2021 High

    PIWIL1 was shown to regulate mRNA stability of specific transcripts (BTG2, FBXW7) in glioma stem cells, and to have stage-specific dual roles in spermatids — translational activation in round spermatids and mRNA degradation in late spermatids before APC/C-mediated elimination.

    Evidence siRNA knockdown with RNA-seq and mRNA stability assays in glioma cells; protein interaction and mRNA stability assays with mouse genetic models in spermatids

    PMID:33406417 PMID:35403682

    Open questions at the time
    • Molecular determinants dictating the switch from translational activation to mRNA degradation are uncharacterized
    • Whether piRNAs guide mRNA target selection in glioma cells is unclear
  11. 2022 High

    Reconstitution showed GTSF1 is required to potentiate PIWIL1's weak intrinsic slicer activity into efficient endonuclease function, identifying the missing cofactor that explained why purified PIWI proteins alone cleave poorly.

    Evidence In vitro RNA cleavage reconstitution ± GTSF1, protein interaction assays, mouse genetic models

    PMID:35772669

    Open questions at the time
    • Structural basis for GTSF1-mediated activation of PIWIL1 not determined
    • Whether additional cofactors further modulate cleavage efficiency is unknown
  12. 2023 High

    Systematic mismatch analysis revealed PIWIL1 cleaves partially paired targets without requiring canonical seed pairing, unlike AGO proteins — explaining how the piRNA pathway silences rapidly evolving transposons.

    Evidence In vitro RNA cleavage assays with systematic mismatch panels across multiple PIWI proteins

    PMID:37344600

    Open questions at the time
    • In vivo mismatch tolerance range during transposon silencing not validated
    • Off-target consequences of relaxed specificity not assessed
  13. 2023 High

    PIWIL1 knockout in golden hamsters caused both male and female sterility and partially compensated for PIWIL3 loss in transposon silencing, establishing that PIWIL1 is essential for fertility in both sexes — extending its requirement beyond the male germline.

    Evidence Knockout animal model with expression profiling and phenotypic analysis in both sexes

    PMID:37644029

    Open questions at the time
    • Mechanism of PIWIL1 function in oogenesis not molecularly defined
    • Whether PIWIL1 female requirement is conserved in mice or humans is unknown
  14. 2024 High

    Cryo-EM structures of mammalian piRISCs revealed a wider nucleic-acid-binding channel, extended prearranged seed, and a vertebrate-specific lysine that distorts the seed trajectory, providing the structural basis for enhanced target capture and mismatch tolerance.

    Evidence Cryo-EM structure determination, comparative biochemistry, site-directed mutagenesis

    PMID:38658622

    Open questions at the time
    • Full-length mammalian PIWIL1 piRISC structure with a bound target RNA not yet reported
    • How GTSF1 remodels the active site structurally remains unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include how PIWIL1 transitions between translational activation and mRNA degradation modes during spermiogenesis, the structural mechanism of GTSF1-mediated slicer activation, and the extent to which piRNA-independent functions drive cancer phenotypes in diverse tumor types.
  • No structural model of GTSF1-bound PIWIL1
  • Stage-specific cofactor switching mechanism uncharacterized
  • piRNA-independent oncogenic functions tested in limited cancer types

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0098772 molecular function regulator activity 3 GO:0140098 catalytic activity, acting on RNA 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1474165 Reproduction 4 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 2
Partners
DNMT1GTSF1PNNPRMT5STMN1TDRD2UHRF1
Complex memberships
APC/C (co-activator in cancer)piRISC

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 HIWI (PIWIL1) is specifically expressed in germline cells of the human testis, detectable in spermatocytes and round spermatids during spermatogenesis, and maps to chromosome 12q24.33. The protein shares significant homology with PIWI family members across its entire length, containing conserved PIWI family domains. RT-PCR, immunohistochemistry, chromosomal mapping Oncogene Medium 12037681
2010 PIWI proteins, including PIWIL1, contain symmetrical dimethyl arginines (sDMAs) mediated by the methyltransferase PRMT5, and this modification enables Tudor domain proteins to associate with PIWIL1 through sDMAs in specific combinations to regulate the piRNA pathway. biochemical characterization, protein interaction studies Genes & development Medium 20360382
2014 The MID domain of Piwi proteins (including the crystal structure of the MID domain from a Piwi Argonaute) specifies recognition of 5' uridine (1U-bias) of piRNAs; mutational analyses reveal the importance of 5' end-recognition within the MID domain for piRNA biogenesis in vivo; domain-swapping experiments reveal an unexpected role for the MID-PIWI module in dictating transposon strand-orientation of bound piRNAs. Crystal structure determination, docking experiments, mutational analysis, domain-swapping experiments, in vivo piRNA biogenesis assays RNA (New York, N.Y.) High 24757166
2015 PIWIL1 plays a role in the polarization and radial migration of newborn cortical neurons in the developing cerebral cortex; knockdown via in utero electroporation caused retardation of transition from multipolar to bipolar stage and defective radial migration. Both the PAZ and PIWI domains were required. PIWIL1 regulates expression of microtubule-associated proteins in cortical neurons. In utero electroporation siRNA knockdown, domain analysis, Western blotting for microtubule-associated proteins Molecular brain Medium 26104391
2015 PIWIL1 directly binds Stathmin1 protein, upregulates Stathmin1 expression by inhibiting RLIM (E3 ubiquitin ligase)-mediated ubiquitin degradation, and reduces phosphorylation of Stathmin1 at Ser-16 by inhibiting the interaction between CaMKII and Stathmin1. Through these mechanisms PIWIL1 suppresses microtubule polymerization and promotes cell proliferation and migration. Co-immunoprecipitation, pulldown assay, ubiquitination assay, phosphorylation assay, microtubule polymerization assay, cell proliferation/migration assays Oncotarget Medium 26317901
2015 Endonucleolytic cleavage of a transcript by a cytosolic PIWI results in its entry into primary piRNA processing, triggering generation of non-overlapping, contiguous primary piRNAs in the 3' direction; these piRNAs are loaded into a nuclear PIWI (such as PIWIL1 in mammals), linking cytoplasmic post-transcriptional silencing to nuclear transcriptional repression. piRNA cluster reporter assays, RNA sequencing, genetic manipulation Cell reports Medium 26166577
2017 TDRD2's extended Tudor domain preferentially recognizes an unmethylated arginine-rich sequence from PIWIL1 through an interface of Tudor and staphylococcal nuclease domains; this interaction is methylation-independent. Mutations disrupting the TDRD2-PIWIL1 interaction compromise piRNA maturation via 3'-end trimming in vitro. Crystal structure determination, structural mutagenesis, in vitro piRNA trimming assay, binding studies Proceedings of the National Academy of Sciences of the United States of America High 29118143
2019 UHRF1 interacts with PRMT5 (an arginine methyltransferase that methylates PIWI proteins) and cooperates with the PIWI pathway during spermatogenesis; conditional loss of UHRF1 in postnatal germ cells disrupts this cooperation, leading to DNA hypomethylation, retrotransposon upregulation, DNA damage response activation, and complete male sterility. Conditional knockout mouse, Co-immunoprecipitation, DNA methylation analysis, RNA sequencing Nature communications Medium 31624244
2020 In human pancreatic ductal adenocarcinoma (PDAC) cells lacking piRNAs, PIWIL1 functions as a co-activator of the APC/C E3 ubiquitin ligase complex, which targets Pinin (a cell adhesion protein) for degradation to promote metastasis. This is in contrast to piRNA-dependent PIWIL1 ubiquitination and removal by APC/C during late spermiogenesis, revealing that piRNAs act as a molecular switch controlling whether PIWIL1 is a substrate or co-activator of APC/C. Co-immunoprecipitation, protein interaction assays, in vivo tumor metastasis assays, ubiquitination assays, mass spectrometry Nature cell biology High 32203416
2020 The crystal structure of Drosophila Piwi in complex with endogenous piRNAs (2.9 Å) reveals PIWI-specific structural features including a non-canonical DVDK catalytic tetrad causing absence of slicer activity. Restoration of the canonical DEDH tetrad by mutagenesis confers slicer activity, and the resulting slicer-competent mutant dissociates more readily from less-complementary targets, suggesting Piwi lost slicer activity during evolution to function as an RNA-guided binding platform for co-transcriptional silencing. Cryo-crystallography at 2.9 Å, active-site mutagenesis, RNA cleavage assay Nature communications High 32051406
2021 Mouse MIWI (PIWIL1)/piRNAs play a dual role in mouse spermatids: translationally activating AU-rich element-containing mRNAs in round spermatids and inducing massive mRNA degradation in late spermatids, through interactions with different protein factors in a developmental stage-dependent manner. MIWI is eliminated through the ubiquitin-26S proteasome pathway by APC/C during late spermiogenesis. Protein interaction studies, mRNA stability assays, ubiquitination assays, mouse genetic models Biology of reproduction High 35403682
2021 Piwil1 knockdown in glioma stem-like cells causes global gene expression changes including increased BTG2 and FBXW7 expression, leading to reduced c-Myc and loss of stem cell factors Olig2 and Nestin. Piwil1 regulates mRNA stability of BTG2, FBXW7, and CDKN1B. siRNA knockdown, RNA sequencing, mRNA stability assay, in vivo tumor model Cell reports Medium 33406417
2021 PIWIL1 in hepatocellular carcinoma increases fatty acid metabolism and oxygen consumption, and induces secretion of Complement C3, which mediates recruitment of myeloid-derived suppressor cells (MDSCs) via activated p38 MAPK signaling in MDSCs, initiating immunosuppressive IL-10 expression to promote tumor growth. Overexpression/knockdown, oxygen consumption assay, RNA-seq, MDSC depletion, neutralization antibodies, in vivo tumor growth assays Signal transduction and targeted therapy Medium 33633112
2022 GTSF1 potentiates the weak intrinsic piRNA-directed RNA cleavage activity of PIWI proteins including mouse MIWI (PIWIL1) and MILI, transforming them into efficient endoribonucleases; GTSF1 is a PIWI-associated auxiliary protein required for piRNA-guided slicer activity. In vitro RNA cleavage assay, protein-protein interaction assays, mouse genetic models Nature High 35772669
2023 Unlike AGO proteins, PIWI proteins (including mouse MIWI/PIWIL1 and human HILI) efficiently cleave transcripts that are only partially paired to their piRNA guides, tolerate mismatches to any target nucleotide including those flanking the scissile phosphate, and do not require canonical seed pairing for binding or cleavage. These relaxed targeting rules allow PIWI proteins to silence newly acquired or rapidly diverging transposons. In vitro RNA cleavage assays with mismatched targets, target binding measurements, comparison across multiple PIWI proteins from different species Nature High 37344600
2024 Cryo-EM structures of mouse MILI and human HILI (PIWIL2/PIWIL1 family) piRISCs reveal a wider nucleic-acid-binding channel and extended prearranged piRNA seed compared to invertebrate counterparts, enabling more efficient target capture. A vertebrate-specific lysine distorts the piRNA seed trajectory toward the PAZ lobe, and functional analyses confirm this lysine promotes target binding and cleavage. The seed gate adopts a relaxed state in mammalian piRISC, explaining how MILI and HILI tolerate seed-target mismatches. Cryo-EM structure determination, comparative biochemical assays (binding and cleavage), site-directed mutagenesis Nature structural & molecular biology High 38658622
2015 Piwil1 in endometrial cancer promotes loss of PTEN expression by upregulating DNMT1, which mediates PTEN promoter hypermethylation; silencing DNMT1 reverses PTEN methylation, establishing a Piwil1→DNMT1→PTEN methylation axis. siRNA knockdown, bisulfite sequencing of PTEN promoter, Western blotting, qRT-PCR Biochemical and biophysical research communications Medium 26056945
2012 Hiwi (PIWIL1) overexpression in sarcoma precursors inhibits their differentiation in vitro, generates sarcomas in vivo in transgenic mice, and its downregulation inhibits growth and re-establishes differentiation. Hiwi-associated tumorigenesis is linked to DNA hypermethylation and silencing of cyclin-dependent kinase inhibitors (CDKIs); DNA methyltransferase inhibitors reverse Hiwi-induced DNA hypermethylation and tumorigenesis. Overexpression/knockdown in cell lines, transgenic mouse model, DNA methylation analysis, DNMT inhibitor treatment PloS one Medium 22438986
2019 Viral-mediated knockdown of Piwil1 in the dorsal hippocampus of adult mice leads to enhanced contextual fear memory without affecting generalized anxiety, implicating Piwil1 in behavioral regulation in the adult mammalian brain, likely through modulation of plasticity-related gene expression. Viral-mediated gene knockdown (in vivo), contextual fear conditioning behavioral assay Neurobiology of learning and memory Medium 30965112
2019 In colorectal cancer (COLO 205) cells, PIWIL1 localizes in a nuage-like structure in the perinuclear region; RNA immunoprecipitation demonstrates that several piRNAs are loaded into PIWIL1 to form complexes that also include their target mRNAs encoding key regulatory proteins involved in colorectal carcinogenesis. Subcellular fractionation/immunofluorescence, RNA immunoprecipitation, RNA sequencing Cells Medium 31694219
2023 In golden hamsters, PIWIL1 is highly expressed throughout oogenesis and early embryogenesis; knockout of PIWIL1 leads to female sterility. PIWIL1 can partially compensate for transposable element silencing in PIWIL3 knockout females. Loss of PIWIL1 in testes also leads to sterility with distinct spermatogenesis disorders. Knockout animal model, expression profiling, subcellular localization studies Nature communications High 37644029

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 PIWI-interacting RNAs: small RNAs with big functions. Nature reviews. Genetics 840 30446728
2007 The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science (New York, N.Y.) 804 17975059
2015 PIWI-Interacting RNA: Its Biogenesis and Functions. Annual review of biochemistry 549 25747396
2014 PIWI proteins and PIWI-interacting RNAs in the soma. Nature 328 24429634
2019 The emerging role of the piRNA/piwi complex in cancer. Molecular cancer 267 31399034
2002 Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene 242 12037681
2022 Emerging roles and functional mechanisms of PIWI-interacting RNAs. Nature reviews. Molecular cell biology 209 36104626
2019 Piwi/PRG-1 Argonaute and TGF-β Mediate Transgenerational Learned Pathogenic Avoidance. Cell 194 31178117
2015 Piwi proteins and piRNAs in mammalian oocytes and early embryos. Cell reports 180 25818294
2010 How does the royal family of Tudor rule the PIWI-interacting RNA pathway? Genes & development 159 20360382
2006 Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. International journal of cancer 151 16287078
2015 Silencio/CG9754 connects the Piwi-piRNA complex to the cellular heterochromatin machinery. Genes & development 139 26494711
2013 PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells. Proceedings of the National Academy of Sciences of the United States of America 125 24367095
2012 Piwis and piwi-interacting RNAs in the epigenetics of cancer. Journal of cellular biochemistry 125 21928326
2015 PIWI Slicing and RNA Elements in Precursors Instruct Directional Primary piRNA Biogenesis. Cell reports 117 26166577
2014 The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic acids research 116 25038252
2015 Slicing and Binding by Ago3 or Aub Trigger Piwi-Bound piRNA Production by Distinct Mechanisms. Molecular cell 111 26340424
2013 Beyond transposons: the epigenetic and somatic functions of the Piwi-piRNA mechanism. Current opinion in cell biology 111 23465540
2017 PIWI-Interacting RNA in Drosophila: Biogenesis, Transposon Regulation, and Beyond. Chemical reviews 92 29281264
2013 Untangling the web: the diverse functions of the PIWI/piRNA pathway. Molecular reproduction and development 86 23712694
2019 UHRF1 suppresses retrotransposons and cooperates with PRMT5 and PIWI proteins in male germ cells. Nature communications 71 31624244
2014 The MID-PIWI module of Piwi proteins specifies nucleotide- and strand-biases of piRNAs. RNA (New York, N.Y.) 71 24757166
2023 Relaxed targeting rules help PIWI proteins silence transposons. Nature 69 37344600
2012 Hiwi mediated tumorigenesis is associated with DNA hypermethylation. PloS one 64 22438986
2021 The biogenesis and biological function of PIWI-interacting RNA in cancer. Journal of hematology & oncology 63 34118972
2020 Functions of PIWI Proteins in Gene Regulation: New Arrows Added to the piRNA Quiver. Trends in genetics : TIG 59 32951946
2023 The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers. Molecular cancer 58 36882835
2016 Abundant and Altered Expression of PIWI-Interacting RNAs during Cardiac Hypertrophy. Heart, lung & circulation 57 27067666
2020 Crystal structure of Drosophila Piwi. Nature communications 56 32051406
2020 piRNA-independent function of PIWIL1 as a co-activator for anaphase promoting complex/cyclosome to drive pancreatic cancer metastasis. Nature cell biology 56 32203416
2021 Terminal modification, sequence, length, and PIWI-protein identity determine piRNA stability. Molecular cell 53 34626567
2015 Emerging roles for PIWI proteins in cancer. Acta biochimica et biophysica Sinica 52 25854579
2021 PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma. Signal transduction and targeted therapy 51 33633112
2019 The emerging roles of PIWI-interacting RNA in human cancers. Cancer management and research 51 31303794
2022 GTSF1 accelerates target RNA cleavage by PIWI-clade Argonaute proteins. Nature 50 35772669
2012 Concise review: The Piwi-piRNA axis: pivotal beyond transposon silencing. Stem cells (Dayton, Ohio) 50 22996918
2014 Silencing HIWI suppresses the growth, invasion and migration of glioma cells. International journal of oncology 48 25269862
2015 Piwi proteins and piRNAs in mammalian oocytes and early embryos: From sample to sequence. Genomics data 47 26484274
2014 Hiwi facilitates chemoresistance as a cancer stem cell marker in cervical cancer. Oncology reports 47 25119492
2021 Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression. Cell reports 44 33406417
2015 Novel function of PIWIL1 in neuronal polarization and migration via regulation of microtubule-associated proteins. Molecular brain 42 26104391
2017 PIWI family emerging as a decisive factor of cell fate: An overview. European journal of cell biology 41 28993008
2017 The meaning of PIWI proteins in cancer development. Oncology letters 40 28529570
2015 Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer. Biochemical and biophysical research communications 39 26056945
2015 Stem cell protein Piwil1 endowed endometrial cancer cells with stem-like properties via inducing epithelial-mesenchymal transition. BMC cancer 38 26506848
2020 Role of PIWI-interacting RNAs on cell survival: Proliferation, apoptosis, and cycle. IUBMB life 37 32697419
2017 The Piwi-piRNA pathway: road to immortality. Aging cell 37 28653810
2014 Hiwi downregulation, mediated by shRNA, reduces the proliferation and migration of human hepatocellular carcinoma cells. Molecular medicine reports 37 25370791
2010 Expression of PSCA, PIWIL1, and TBX2 in endometrial adenocarcinoma. Onkologie 37 20502058
2021 An old weapon with a new function: PIWI-interacting RNAs in neurodegenerative diseases. Translational neurodegeneration 36 33685517
2017 MiRNA-154-5p inhibits cell proliferation and metastasis by targeting PIWIL1 in glioblastoma. Brain research 35 28842123
2016 PIWI-Interacting RNAs in Gliomagenesis: Evidence from Post-GWAS and Functional Analyses. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 33 27197292
2014 Overexpression of hiwi promotes growth of human breast cancer cells. Asian Pacific journal of cancer prevention : APJCP 33 25292027
2018 PIWI-piRNA pathway: Setting the pace of aging by reducing DNA damage. Mechanisms of ageing and development 32 29580825
2023 The burgeoning importance of PIWI-interacting RNAs in cancer progression. Science China. Life sciences 31 38198029
2019 PIWI-interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells. Journal of cellular physiology 31 31478570
2015 A piece of the pi(e): The diverse roles of animal piRNAs and their PIWI partners. Seminars in cell & developmental biology 31 26582251
2010 The universal overexpression of a cancer testis antigen hiwi is associated with cancer angiogenesis. Oncology reports 31 20204292
2018 Epigenetic roles of PIWI‑interacting RNAs (piRNAs) in cancer metastasis (Review). Oncology reports 29 30226604
2017 Structural basis for arginine methylation-independent recognition of PIWIL1 by TDRD2. Proceedings of the National Academy of Sciences of the United States of America 29 29118143
2021 PIWI-mediated control of tissue-specific transposons is essential for somatic cell differentiation. Cell reports 28 34610311
2021 A Review of Discovery Profiling of PIWI-Interacting RNAs and Their Diverse Functions in Metazoans. International journal of molecular sciences 27 34681826
2024 Critical appraisal of the piRNA-PIWI axis in cancer and cancer stem cells. Biomarker research 26 38303021
2021 The Emerging Role of PIWI-Interacting RNAs (piRNAs) in Gastrointestinal Cancers: An Updated Perspective. Cancers 26 35008366
2023 What Are the Functional Roles of Piwi Proteins and piRNAs in Insects? Insects 25 36835756
2023 PIWI-interacting RNAs: Critical roles and therapeutic targets in cancer. Cancer letters 25 37076042
2021 Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility. Nature communications 25 33658512
2019 Disrupting the hippocampal Piwi pathway enhances contextual fear memory in mice. Neurobiology of learning and memory 25 30965112
2024 Mammalian PIWI-piRNA-target complexes reveal features for broad and efficient target silencing. Nature structural & molecular biology 24 38658622
2020 PIWI-interacting RNAs: Mitochondria-based biogenesis and functions in cancer. Genes & diseases 23 34291132
2018 Investigation of piwi-interacting RNA pathway genes role in idiopathic non-obstructive azoospermia. Scientific reports 23 29317647
2013 Elevated expression of Piwi and piRNAs in ovaries of triploid crucian carp. Molecular and cellular endocrinology 23 24316377
2011 Gatekeepers for Piwi-piRNA complexes to enter the nucleus. Current opinion in genetics & development 23 21764576
2024 AVCAPIR: A Novel Procalcific PIWI-Interacting RNA in Calcific Aortic Valve Disease. Circulation 22 38258575
2014 HITS-CLIP (CLIP-Seq) for mouse Piwi proteins. Methods in molecular biology (Clifton, N.J.) 22 24178558
2012 Altered expression of porcine Piwi genes and piRNA during development. PloS one 22 22952772
2018 Investigating piwi-interacting RNA regulome in human neuroblastoma. Genes, chromosomes & cancer 21 29516567
2015 MicroRNA let-7a modifies the effect of self-renewal gene HIWI on patient survival of epithelial ovarian cancer. Molecular carcinogenesis 21 25630839
2015 Hiwi Promotes the Proliferation of Colorectal Cancer Cells via Upregulating Global DNA Methylation. Disease markers 21 26355242
2022 piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis. Molecular neurobiology 20 35015250
2019 Molecular and Functional Characterization of the Somatic PIWIL1/piRNA Pathway in Colorectal Cancer Cells. Cells 20 31694219
2018 Two distinct transcriptional controls triggered by nuclear Piwi-piRISCs in the Drosophila piRNA pathway. Current opinion in structural biology 20 29990672
2017 Drosophila PAF1 Modulates PIWI/piRNA Silencing Capacity. Current biology : CB 20 28844648
2017 The PIWI-Interacting RNA Molecular Pathway: Insights From Cultured Silkworm Germline Cells. BioEssays : news and reviews in molecular, cellular and developmental biology 20 29164638
2021 Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications. Frontiers in cell and developmental biology 19 33718392
2019 Epigenetic roles of PIWI proteins and piRNAs in lung cancer. Cell & bioscience 19 31890151
2017 Altered microRNA and Piwi-interacting RNA profiles in cumulus cells from patients with diminished ovarian reserve. Biology of reproduction 19 28651359
2020 DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans. Nature communications 17 32843637
2020 Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways. Cells 17 32992598
2020 Effects of fluoride on PIWI-interacting RNA expression profiling in testis of mice. Chemosphere 17 33213873
2018 The nucleolar transcriptome regulates Piwi shuttling between the nucleolus and the nucleoplasm. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 17 30539407
2015 PIWIL1 destabilizes microtubule by suppressing phosphorylation at Ser16 and RLIM-mediated degradation of Stathmin1. Oncotarget 17 26317901
2023 PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease. Nature communications 16 37783675
2022 PiWi RNA in Neurodevelopment and Neurodegenerative Disorders. Current molecular pharmacology 16 34212832
2017 Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells. The Journal of clinical investigation 16 28920925
2013 Fighting an old war with a new weapon--silencing transposons by Piwi-interacting RNA. IUBMB life 16 23893818
2023 The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters. Nature communications 15 37644029
2022 Noncanonical functions of PIWIL1/piRNAs in animal male germ cells and human diseases†. Biology of reproduction 15 35403682
2015 The clinical significances of the abnormal expressions of Piwil1 and Piwil2 in colonic adenoma and adenocarcinoma. OncoTargets and therapy 15 26064060
2013 Identification and expression pattern analysis of Piwi genes during the spermiogenesis of Portunus trituberculatus. Gene 15 24211384