PIWI family emerging as a decisive factor of cell fate: An overview

Ponnusamy, Murugavel; Yan, Kao Wen; Liu, Cui-Yun; Li, Peifeng; Wang, Kun

doi:10.1016/j.ejcb.2017.09.004

Cited by 43 publications

(37 citation statements)

References 125 publications

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“…16 PIWI proteins and PIWI-interacting RNAs participate in many vital biological processes, including cell proliferation, migration, survival, and inflammation. 17,18 Hence, their involvement in wound healing and tissue regeneration does not come as a surprise. 17 Although its highest expression is observed in germline tissue, PIWIL1 has been reported along the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 Hence, their involvement in wound healing and tissue regeneration does not come as a surprise. 17 Although its highest expression is observed in germline tissue, PIWIL1 has been reported along the gastrointestinal tract. 19 Existing studies mainly focused on the aberrant expression of PIWIL1 in tumors, 18 but the biological role of PIWIL1 in IBD has never been elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Expression Levels of 4 Genes in Colon Tissue Might Be Used to Predict Which Patients Will Enter Endoscopic Remission After Vedolizumab Therapy for Inflammatory Bowel Diseases

Verstockt

Veny

et al. 2020

Clinical Gastroenterology and Hepatology

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BACKGROUND & AIMS: We aimed to identify biomarkers that might be used to predict responses of patients with inflammatory bowel diseases (IBD) to vedolizumab therapy. METHODS: We obtained biopsies from inflamed colon of patients with IBD who began treatment with vedolizumab (n [ 31) or tumor necrosis factor (TNF) antagonists (n [ 20) and performed RNA-sequencing analyses. We compared gene expression patterns between patients who did and did not enter endoscopic remission (absence of ulcerations at month 6 for patients with Crohn's disease or Mayo endoscopic subscore £1 at week 14 for patients with ulcerative colitis) and performed pathway analysis and cell deconvolution for training (n [ 20) and validation (n [ 11) datasets. Colon biopsies were also analyzed by immunohistochemistry. We validated a baseline gene expression pattern associated with endoscopic remission after vedolizumab therapy using 3 independent datasets (n [ 66). RESULTS: We identified significant differences in expression levels of 44 genes between patients who entered remission after vedolizumab and those who did not; we found significant increases in leukocyte migration in colon tissues from patients who did not enter remission (P < .006). Deconvolution methods identified a significant enrichment of monocytes (P [ .005), M1macrophages (P [ .05), and CD4D T cells (P [ .008) in colon tissues from patients who did not enter remission, whereas colon tissues from patients in remission had higher numbers of naïve B cells before treatment (P [ .05). Baseline expression levels of PIWIL1, MAATS1, RGS13, and DCHS2 identified patients who did vs did not enter remission with 80% accuracy in the training set and 100% accuracy in validation dataset 1. We validated these findings in the 3 independent datasets by microarray, RNA sequencing and quantitative PCR analysis (P [ .003). Expression levels of these 4 genes did not associate with response to anti-TNF agents. We confirmed the presence of proteins encoded by mRNAs using immunohistochemistry. CONCLUSIONS: We identified 4 genes whose baseline expression levels in colon tissues of patients with IBD associate with endoscopic remission after vedolizumab, but not anti-TNF, treatment. We validated this signature in 4 independent datasets and also at the protein level. Studies of these genes might provide insights into the mechanisms of action of vedolizumab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expression Levels of 4 Genes in Colon Tissue Might Be Used to Predict Which Patients Will Enter Endoscopic Remission After Vedolizumab Therapy for Inflammatory Bowel Diseases

Verstockt

Veny

et al. 2020

Clinical Gastroenterology and Hepatology

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“…Non-LTR families L1, SVA, and Alu were found to be upregulated in breast, ovarian, colon, and hematological cancers [137]; (3) the third subclass is composed of inactive LTR retrotransposons resulting from ancient germline retroviral infections. Within the human genome, only 80-100 TEs among LINE sequences are competent for the entire retrotransposition activity [8]. In the germline, TEs represent pivotal actors implicated in the shaping of genomes during evolution, and presence of retrotransposition in numerous somatic cells indicates that TEs contribute to edification of mosaicism.…”

Section: Maintenance Of Genome Stability and Integritymentioning

confidence: 99%

“…Large-scale genomic technologies have provided an astonishing insight into human genome and transcriptome. Next-generation sequencing techniques combined with bioinformatics have revealed that more than 50% of mammalian genomes were composed of TEs and that more than 98% of the human genome was actively transcribed [8]. However, only 1.1% of the genome encodes proteins, and a majority of genes are noncoding RNAs (ncRNAs) [9].…”

Section: Introductionmentioning

confidence: 99%

Part 1: The PIWI-piRNA Pathway Is an Immune-Like Surveillance Process That Controls Genome Integrity by Silencing Transposable Elements

Meseure¹,

Alsibai²

2020

Chromatin and Epigenetics

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PiRNAs [P-element-induced wimpy testis (PIWI)-interacting RNAs] represent the most frequent but the least well-investigated subtype of small ncRNAs and are characterized by their interaction with PIWI proteins, a subclass of the Argonaute family. PiRNAs and PIWI proteins maintain integrity of the genomic structure and regulate gene expression in germline and somatic cells. The PIWI-piRNA pathway primarily constitutes a conserved immune-like surveillance process that recognizes self and nonself. This axis controls genome integrity of germline cells and nonaging somatic cells by silencing and suppressing propagation of transposable elements through epigenetic and posttranscriptional mechanisms. However, mounting evidences indicate that the PIWI-piRNA pathway has broader implications in both germinal and somatic cells in various physiological and pathological processes. It modulates mRNAs levels of expression, stability, turnover, and translation and interacts directly with many transcription factors and signaling pathways molecules. PIWI proteins and piRNAs play pivotal roles in germline stem cell maintenance and self-renewal, fertilization and development, genes and proteins expression, genome rearrangement, and homeostasis.

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“…In addition to their role in germline genome defence, there is a growing recognition that the Piwi pathway is involved in cell fate decisions during development and throughout the lifespan (Ponnusamy, Yan, Liu, Li, and Wang, 2017). This function extends to neuronal precursors; Piwil1 is involved in the polarisation and radial migration of neurons in the mouse fetal cerebral cortex, partly through its effect on the expression of microtubule-associated proteins (Zhao, Yao, Chang, Gou, Liu, Qiu, and Yuan, 2015), and the neocortical circuitry is disrupted in the Piwil1 knock-out mouse model, compromising development (Viljetic, Diao, Liu, Krsnik, Wijeratne, Kristopovich, Dutre-Clarke, Kraushar, Song, and Xing, 2017).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal knockdown of Piwil1 and Piwil2 enhances contextual fear memory in mice

Leighton

Wei

et al. 2018

Preprint

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The Piwi pathway is a conserved gene regulatory mechanism comprised of Piwi-like proteins and Piwiinteracting RNAs, which modulates gene expression via RNA interference and epigenetic mechanisms.The mammalian Piwi pathway has been defined by its role in transposon control during spermatogenesis, and despite an increasing number of studies demonstrating its expression in the nervous system, relatively little is known about its function in neurons or potential contribution to gene regulation in the brain. We have discovered that all three Piwi-like genes are expressed in several regions of the mouse brain, and that simultaneous knockdown of Piwil1 and Piwil2 in the adult mouse hippocampus enhances contextual fear memory without affecting generalised anxiety. Our results implicate the Piwi pathway in control of plasticity-related gene expression in the adult mammalian brain.

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PIWI family emerging as a decisive factor of cell fate: An overview

Cited by 43 publications

References 125 publications

Expression Levels of 4 Genes in Colon Tissue Might Be Used to Predict Which Patients Will Enter Endoscopic Remission After Vedolizumab Therapy for Inflammatory Bowel Diseases

Expression Levels of 4 Genes in Colon Tissue Might Be Used to Predict Which Patients Will Enter Endoscopic Remission After Vedolizumab Therapy for Inflammatory Bowel Diseases

Part 1: The PIWI-piRNA Pathway Is an Immune-Like Surveillance Process That Controls Genome Integrity by Silencing Transposable Elements

Hippocampal knockdown of Piwil1 and Piwil2 enhances contextual fear memory in mice

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