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Predicting piRNA-Disease Associations Based on Dual-View Learning and Multi-head Self-Attention Mechanism Fusion.

PIWI-interacting RNAs (piRNAs) are an important class of non-coding RNA molecules in epigenetic regulation. It plays a crucial role in maintaining genomic stability and inhibiting transposable elements, and have been proven to participate in various diseases by regulating gene expression and influencing signaling pathways. Traditional biological experimental methods have limitations such as low throughput, long cycles, and high costs, making them difficult to meet the requirements of large-scale systematic screening. In this study, we develop a predictive framework named PiDA-DVLSA. We integra…

PiRNA hsa_pir_018849 promotes the proliferation and invasion of osteosarcoma cells by regulating the stability of CCN5 mRNA.

BACKGROUND: Osteosarcoma is a primary malignant bone tumor and that is predominantly found in adolescents and young adults, and it often occurs during periods of rapid bone growth. The precise specific etiology of osteosarcoma remains largely unknown. Piwi-interacting RNAs (piRNAs) are a class of small noncoding RNAs that are typically 24 to 31 nucleotides long, and they have potential therapeutic applications in diseases. METHODS: Small RNA sequencing and qPCR were initially used to detect differentially expressed piRNAs in the MG63 osteosarcoma cell line and in osteosarcoma tissues. The exp…

piR-hsa-022095 Drives Hypertrophic Scar Formation via KLF11-Dependent Fibroblast Proliferation.

Background/Objectives: Hypertrophic scar (HS) is a fibroproliferative disorder characterized by excessive fibroblast activation and collagen deposition. The role of PIWI-interacting RNAs (piRNAs) in HS pathogenesis has not been defined. This study aimed to identify HS-related piRNAs, clarify their molecular mechanisms, and evaluate their therapeutic potential. Methods: High-throughput piRNA sequencing was performed on hypertrophic scar and matched normal tissues, followed by validation in patient-derived samples and dermal fibroblasts using quantitative reverse transcription PCR. Functional as…

A putative PIWIL/piRNA-OTX2 network: An emerging model for epigenetic regulation of cancer stemness in retinoblastoma.

Recent findings underscore the critical role of PIWIL/piRNA pathways in cancer, extending their known functions beyond reproductive biology. Retinoblastoma (RB), a rare pediatric retinal tumor, is primarily driven by RB1 gene loss but also involves significant epigenetic alterations. Our previous studies revealed that PIWIL4 is significantly upregulated in RB, and its knockdown disrupts the expression of stemness-associated factors, including OTX2, SOX2, and NANOG. In this review, we have proposed that PIWIL/piRNA complexes might recruit epigenetic modifiers to cis-regulatory modules (CRMs) of

Ethylene glycol monomethyl ether altered rat sperm small RNAs with critical developmental roles.

Ethylene glycol monomethyl ether (EGME) is a testicular germ cell toxicant that selectively targets spermatocytes. In rats, male-only EGME exposure reduces mating success and can lead to an increase in resorbed fetuses. In a previous study, 5-d exposure to 50, 60, or 75 mg/kg/d EGME in male rats led to a decrease in sperm motility and increase in retained spermatid heads with a lowest observed adverse effect level (LOAEL) of 75 mg/kg/d. At 60 mg/kg/d, EGME exposure altered the proportion of sperm small RNA reads mapped to different small RNA categories and the distribution of read lengths. To

piRNA-mediated silencing of exogenous retrovirus in mouse spermatogonial stem cells.

Viral integration into germline cells poses a transgenerational threat to genome stability, yet protective mechanisms remain unclear. We demonstrate that Trp53 and PIWI-interacting RNAs (piRNAs) are essential for antiviral defense through regulation of the cancer-testis antigen MAGEA5. Transient viral infection in spermatogonial stem cells (SSCs) induces piRNAs, which are perturbed in Trp53-or Piwil2-deficient SSCs. This disruption increases viral expression and reduces histone H3 lysine 9 trimethylation and DNA methylation at long terminal repeats. Antisense piRNA production is largely absent…

Maternal ovo represses the expression of transposable elements in adult ovaries.

In germ cells, repressing transposable elements (TEs) is important to maintain genomic integrity. TE expression and transposition are repressed by PIWI-interacting RNAs (piRNAs). Although many genes for piRNA synthesis have been described, few transcription factors activating their expression have been identified. We previously reported that a transcription factor, maternal Ovo (Ovo-B) protein activates germline-specific gene expression in progenitors of germ cells. In this study, we found that maternal Ovo also activates several genes, including aubergine (aub), for TE silencing. Knocking dow…

Differential expression of small RNA pathway genes associated with the Biomphalaria glabrata/Schistosoma mansoni interaction.

The World Health Organization (WHO) estimates that approximately 240 million people in 78 countries require treatment for schistosomiasis, an endemic disease caused by trematodes of the genus Schistosoma. In Brazil, Schistosoma mansoni is the only species representative of the genus whose passage through an invertebrate host, snails of the genus Biomphalaria, is obligatory before infecting a mammalian host, including humans. The availability of the genome and transcriptome of B. glabrata makes studying the regulation of gene expression, particularly the regulation of miRNA and piRNA processing

Small non-coding RNA profiling in patients with non-muscle invasive bladder cancer.

The intricate regulatory roles of small non-coding RNAs (sncRNAs), including PIWI-interacting RNAs (piRNAs) and microRNAs (miRNAs), have been increasingly recognized in the modulation of cellular functions and are associated with the pathogenesis of various diseases, notably cancer. However, the specific dysregulation patterns of sncRNAs in non-muscle-invasive bladder cancer (NMIBC) have yet to be fully delineated, highlighting a significant gap in our current understanding. To elucidate the expressional dynamics of sncRNAs for patients with NMIBC, we characterized the profile of piRNAs and mi…

Novel PNLDC1 mutations underlie nonobstructive azoospermia in humans and mice.

PIWI-interacting RNAs (piRNAs) are small regulatory RNAs (21-35 nucleotides) exclusively expressed in germ cells, where they play a critical role in transposable element repression and post-meiotic gene regulation. The poly(A)-specific RNase-like domain-containing 1 (PNLDC1) protein is essential for piRNA maturation, specifically in 3'-end trimming. Disruption of PNLDC1 has been implicated in nonobstructive azoospermia (NOA) and male infertility. Through whole-exome sequencing, we identified a compound heterozygous mutation (MT1 c.449G > A, p.Trp150* and MT2 c.821A > G, p.His274Ala) in a Chine…

Role of piRNA biogenesis and its neuronal function in the development of neurodegenerative diseases.

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by neuronal loss and dysfunction. Despite remarkable improvements in our understanding of these pathogeneses, serious worldwide problems with significant public health burdens are remained. Therefore, new efficient diagnostic and therapeutic strategies are urgently required. PIWI-interacting RNAs (piRNAs) are a major class of small non-coding RNAs that silence gene expression through transcriptional and post-transcriptional processes. Recent studies have d…

Next-generation sequencing reveals aqueous MicroRNA and piRNA signatures in age-related macular degeneration and polypoidal choroidal vasculopathy.

MicroRNAs (miRNAs) play important roles in the pathogenesis of age-related macular degeneration (AMD), while whether polypoidal choroidal vasculopathy (PCV) represents a subtype of AMD remains controversial. However, the differential small non-coding RNA profiles in aqueous humor (AH) between neovascular AMD (nAMD) and PCV remain insufficiently characterized. Therefore, this study aimed to characterize miRNA and piRNA expression profiles in AH samples from nAMD and PCV patients and to explore the potential involvement of these small non-coding RNAs in angiogenesis-related pathways. AH samples

Paternal cytokine administration alters sperm small ncRNAs and offspring brain and behavior.

Paternal pre-conceptual exposure to pathogenic infection can alter offspring phenotypes via changes to sperm epigenetics, including small non-coding RNAs (ncRNAs). This phenomenon occurs even in the absence of infection when pathogen mimetics trigger paternal immune activation (PIA). While this implicates a shared component of the immune response, the specific mechanisms responsible remain unknown. Cytokines are a key component of innate immunity and are highly upregulated following exposure to both pathogens and their mimetics. Here we investigate whether paternal administration of the pro-in

Triple‑negative breast cancer cell‑derived piR‑31115 promotes the proliferation and migration of endothelial cells via METTL3‑mediated m6A modification of YAP1.

Triple‑negative breast cancer (TNBC), a highly malignant breast cancer subtype with a pronounced metastatic propensity, forms the focus of the present investigation. MDA‑MB‑231, a prevalently utilized TNBC cell line in cancer research, was employed. In accordance with the tumour angiogenesis theory, cancer cells are capable of instigating angiogenesis and the formation of a novel vascular system within the tumour microenvironment, which subsequently sustains malignant proliferation and metastasis. Consequently, impeding the growth of tumour blood vessels holds substantial significance in suppr

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… *P<0.05 and ***P<0.001. piR, Piwi-interacting RNA; RT-qPCR, reverse transcription-quantitative PCR; CM, conditioned medium; NC, negative control; LV, lentivirus; NS, not significant. … Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer. Mol Cancer. 2018;17:16. doi: 10.1186/s12943-018-0767-3. 20. …

Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility.

BACKGROUND: Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate a host of crucial cellular processes like proliferation, differentiation and apoptosis by regulating gene expression. While small noncoding RNAs (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting RNAs have been extensively studied in male germ cell development, the role of lncRNAs in spermatogenesis remains largely unknown. OBJECTIVE: In this article, we have reviewed the biology and role of lncRNAs in spermatogenesis along with the tools available for data analysis. RESULTS AND CONCLUSIONS: T…

Transposable element expansion and low-level piRNA silencing in grasshoppers may cause genome gigantism.

BACKGROUND: Transposable elements (TEs) have been likened to parasites in the genome that reproduce and move ceaselessly in the host, continuously enlarging the host genome. However, the Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of TE invasion by imposing small-RNA-mediated silencing. Here we compare the TE activity of two grasshopper species with different genome sizes in Acrididae (Locusta migratoria manilensis♀1C = 6.60 pg, Angaracris rhodopa♀1C = 16.36 pg) to ascertain the influence of piRNAs. RESULTS: We discovered that repetitive sequen…

Changes of small non-coding RNAs by severe acute respiratory syndrome coronavirus 2 infection.

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome co … ost-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we recently found that nasopharyngeal swabs (NPS) sa …

Insulator BEAF32 regulates expression of tissue-specific genes and piRNA source loci in Drosophila ovaries.

BACKGROUND: Insulators are the multifunctional DNA binding proteins that perform architectural functions and regulate gene transcription. Al … ssion for the cell-cycle regulatory kinase, Polo. To investigate the possible role of BEAF32 in the Piwi-interacting RNAs (piRNAs) pathway we analyzed ovarian small RNAs in BEAF32 null mutants and found a strong decrease in the production of piRNAs from the 3R subtelomeric region. Our data suggest that the BEAF32-containing chromatin complex located upstream of the su …

piR-1170 drives brain metastasis and immune evasion via WTAP-mediated m6A methylation reprogramming in triple-negative breast cancer.

Therapeutic target for triple-negative breast cancer (TNBC) brain metastases remains a critical unmet clinical challenge. The roles of PIWI-interacting RNAs (piRNAs) in driving brain metastasis are poorly understood, despite their known dysregulation and oncogenic functions in cancer. Here, we identified piR-1170 as a clinically relevant driver of TNBC brain metastasis through multi-model validation. Analysis of the TNBC cohort from Sun Yat-sen University Cancer Center revealed significant piR-1170 upregulation in brain metastases correlating with poor patient survival. First, upstream analysi…

mRNA and P-element-induced wimpy testis-interacting RNA profile in chemical-induced oral squamous cell carcinoma mice model.

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs), a novel class of noncoding RNAs, are involved in the carcinogenesis. However, the functional significance of piRNAs in oral squamous cell carcinoma (OSCC) remains unknown. In the present study, we used chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) induced OSCC mouse model. piRNAs and mRNAs were profiled using next-generation sequencing in the tongue tumor tissues from 4NQO induction and healthy tongue tissues from control mice. Furthermore, we analyzed the differential gene expression of human OSCC in Gene Expression Omnibu