PIWIL4 knockdown alters piRNA expression in RSV-infected immortalized small airway epithelial cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE341204 | GEO | 2026/07/28
REPOSITORIES: GEO
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Project description:Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children, the elderly, and immunocompromised hosts, and no effective vaccine or therapy exists for infants. PIWIL4, a member of the PIWI protein family known to interact with PIWI-interacting RNAs (piRNAs), was found to be induced by RSV infection in airway epithelial cells. To investigate the role of PIWIL4 in the transcriptional response to RSV, immortalized small airway epithelial (iSAE) cells were transfected with either a non-targeting or a PIWIL4-targeting siRNA and then left uninfected or infected with RSV for 15 hours. Gene expression was profiled using the Agilent Whole Human Genome Oligo Microarray (4x44K) to identify genes differentially expressed upon PIWIL4 knockdown under basal and RSV-infected conditions. 4 samples, one array per condition (no biological replicate arrays; RNA from three pooled technical replicate wells per condition was hybridized to a single array). 2x2 factorial design: siRNA treatment (non-targeting control vs. PIWIL4-targeting) x infection status (uninfected control vs. RSV Long strain infection, MOI 5, 15 hours post-infection) in immortalized human small airway epithelial (iSAE) cells.
2026-07-28 | GSE341202 | GEO
Project description:PIWI proteins bind to PIWI-interacting RNAs (piRNAs) and play key roles in the biogenesis and functions of piRNAs. It has been reported that PIWI proteins are essential for stem cell self-renewal and germline development in diverse organisms, and are ectopically expressed in multiple forms of cancer. However, the role of PIWI in cancer remains elusive. Here we report that one of the four PIWI proteins in humans, PIWIL4, is highly expressed in both breast cancer tissues and the cytoplasm of MDA-MB-231 cell line derived from breast cancer. Reducing PIWIL4 expression drastically impairs migration ability of MDA-MB-231 cells, significantly increases their apotosis, and mildly affects their proliferation. Our transcriptome and proteome analyses reveal that these functions are at least partially achieved via the PIWIL4 regulation of TGF-beta and FGF signaling pathways and major histocompatibility complex (MHC) class II proteins. These findings suggest that PIWIL4 may serve as a potential therapeutic target for breast cancer. Examination of small RNAs in two conditions
2016-03-08 | E-GEOD-78238 | biostudies-arrayexpress
Project description:PIWI proteins bind to PIWI-interacting RNAs (piRNAs) and play key roles in the biogenesis and functions of piRNAs. It has been reported that PIWI proteins are essential for stem cell self-renewal and germline development in diverse organisms, and are ectopically expressed in multiple forms of cancer. However, the role of PIWI in cancer remains elusive. Here we report that one of the four PIWI proteins in humans, PIWIL4, is highly expressed in both breast cancer tissues and the cytoplasm of MDA-MB-231 cell line derived from breast cancer. Reducing PIWIL4 expression drastically impairs migration ability of MDA-MB-231 cells, significantly increases their apotosis, and mildly affects their proliferation. Our transcriptome and proteome analyses reveal that these functions are at least partially achieved via the PIWIL4 regulation of TGF-beta and FGF signaling pathways and major histocompatibility complex (MHC) class II proteins. These findings suggest that PIWIL4 may serve as a potential therapeutic target for breast cancer.
2016-03-08 | GSE78238 | GEO
Project description:PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that are almost exclusively expressed in germ cells where they work to silence harmful transposons to maintain genomic stability. It is proposed that the associated piRNAs guide the nuclear PIWIL4 to transposable elements where it recruits the DNA methylation apparatus and instructs de novo DNA methylation. Herein we identify a missense variant of PIWIL4 (c.805 C>T p.R269W) in two infertile males. Though male homozygous knock-in mice harboring the orthologous variant exhibit normal sperm counts and morphology, they display increased expression of transposable elements and abnormal gene expression during the first wave of spermatogenesis. Mechanistically, the mutated site impairs the piRNA-binding ability of PIWIL4 and leads to the derepression of some LINE-1 elements. In summary, we have identified a piRNA binding mutation in PIWIL4 that may be involved in human non-obstructive azoospermia.
2025-02-20 | GSE258973 | GEO
Project description:Despite being exposed to respiratory syncytial virus (RSV) infection multiple times in our lives, infants, older-adults, and immunocompromised patients are vulnerable to RSV-associated severe diseases, such as bronchiolitis and pneumonia. Respiratory viral infections are known to promote pulmonary fibrosis formation, which are often associated with a cellular remodeling process epithelial-mesenchymal transition (EMT). However, there is no information on whether RSV causes EMT in bronchial epithelial cells. Our results suggest that RSV-infection does not induce EMT in three different in vitro lung models: epithelial A549 cell line, primary normal human bronchial epithelial cells, and pseudostratified airway epithelium. Interestingly, RSV infection increased cell surface area and perimeter in the infected airway epithelium, which is distinct from the TGF-β1 driven cell elongation. Genome-wide transcriptome analysis also revealed that RSV infection is not involved in cell motility and locomotion. Thus, our results suggest that RSV infection does not induce EMT in the airway epithelium
2023-06-13 | GSE189537 | GEO
Project description:In the male mouse germline, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germline remains unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility. Through the analysis of one of these pathogenic alleles, we discovered that the uncharacterised protein C19ORF84 interacts with SPOCD1. DNMT3C, the DNA methyltransferase responsible for transposon methylation, associates with SPOCD1 and C19ORF84 in foetal gonocytes. Furthermore, C19ORF84 is essential for piRNA-directed DNA methylation and male mouse fertility. Finally, C19ORF84 mediates the in vivo association of SPOCD1 with the de novo methylation machinery. In summary, we have discovered a conserved role for the human piRNA pathway in transposon silencing and C19ORF84, an uncharacterised protein essential for orchestrating piRNA-directed DNA methylation.
2024-02-14 | PXD047331 | Pride
Project description:Senecavirus A (SVA) belongs to the family of small RNA viruses, the genus Senecavirus, and has become a research hotspot because of the oncolytic viral characteristics. PIWI-interacting RNAs (piRNAs) are a class of small RNAs found in mammalian cells in recent years; however, the host piRNA expression profile during SVA infection and their role in viral infection is not well understood. In this study, we obtained small RNA transcriptome expression profiles from SVA-infected pig kidney cell lines (PK-15) by high-throughput sequencing. Differential expression (DE) analysis, GO annotation, and KEGG analysis of piRNAs in SVA-infected and non-infected PK-15 cells were performed. qRT-PCR was used to validate the DE of piRNAs. The results showed that 981 and 1,370 novel piRNAs were identified in SVA-infected and non-infected PK-15 cells; expression of 129 piRNAs was upregulated while that of 44 piRNAs was downregulated after SVA infection. The DE of 10 piRNAs was further verified by qRT-PCR. GO annotation analysis results showed the metabolism, proliferation, and differentiation were significantly activated after SVA infection. KEGG results showed that after SVA infection, piRNA was mainly enriched in AMPK signaling pathway, Rap1 signaling pathway, circadian rhythm, and VEGF signaling pathway, which suggested that piRNAs may play a role in regulating antiviral immunity, intracellular homeostasis, and tumor processes during SVA infection. This is the first report of the piRNA transcriptome in pig kidney cells and will contribute to the research of piRNA regulatory mechanism during SVA infections and provide an important reference for the prevention and treatment of SVA.
2023-01-05 | GSE222010 | GEO
Project description:Piwi-interacting RNAs (piRNAs) are gonad-specific small RNAs that provide defence against transposable genetic elements called transposons. Our knowledge of piRNA biogenesis is sketchy, partly due to an incomplete inventory of the factors involved. Here, we identify Tudor domain-containing 12 (TDRD12; also known as ECAT8) as a novel piRNA biogenesis factor in mice. TDRD12 is detected in complexes containing MILI (PIWIL2), its associated primary piRNAs, and TDRD1, all of which are already implicated in secondary piRNA biogenesis. Male mice carrying either a nonsense point mutation (repro23 mice) or a targeted deletion in the Tdrd12 locus are infertile, and de-repress retrotransposons. We find that TDRD12 is dispensable for primary piRNA biogenesis but essential for production of secondary piRNAs that enter MIWI2 (PIWIL4). Cell culture studies with the insect orthologue of TDRD12 suggest a role for the multi-domain protein in mediating complex formation with other participants during secondary piRNA biogenesis. Total small RNA and immunoprecipitated small RNA were purified from mouse testis extract and Bmn4 cells for preparation of high-throughput sequencing libraries.
2013-11-04 | E-GEOD-50544 | biostudies-arrayexpress
Project description:Piwi-interacting RNAs (piRNAs) are gonad-specific small RNAs that provide defence against transposable genetic elements called transposons. Our knowledge of piRNA biogenesis is sketchy, partly due to an incomplete inventory of the factors involved. Here, we identify Tudor domain-containing 12 (TDRD12; also known as ECAT8) as a novel piRNA biogenesis factor in mice. TDRD12 is detected in complexes containing MILI (PIWIL2), its associated primary piRNAs, and TDRD1, all of which are already implicated in secondary piRNA biogenesis. Male mice carrying either a nonsense point mutation (repro23 mice) or a targeted deletion in the Tdrd12 locus are infertile, and de-repress retrotransposons. We find that TDRD12 is dispensable for primary piRNA biogenesis but essential for production of secondary piRNAs that enter MIWI2 (PIWIL4). Cell culture studies with the insect orthologue of TDRD12 suggest a role for the multi-domain protein in mediating complex formation with other participants during secondary piRNA biogenesis.
2013-11-04 | GSE50544 | GEO
Project description:To investigate how human airway epithelial cells respond to Influenza or RSV infection, we harvested airway epithelial cells from the mainstream bronchi of human donors and cultured them as previously described (Pickles et al,1998) in a polarized system that resembles the in vivo mucociliary pseudostratified epithelium. Quadruplicate hAEC cultures were infected with 2X105 PFUs Influenza A (Udorn) or with 1x106 PFUs RSV for 2h or mock inoculated and harvested 24h after Influenza infection and 48h after RSV infection. Quadruplicate polarized airway epithelial cell cultures were mock treated or infected with 2x10^5 PFUs of Influenza A (Udorn) for 2h or infected with 1x10^6 PFUs RSV and harvested 24 h post infection for Influenza or 48h post infection for RSV. Total RNA was harvested and gene expression was studied using Genespring GX v7.3.1.
2012-03-12 | E-GEOD-32138 | biostudies-arrayexpress