ArticleBiomarker research2025
Piwi-interacting RNA 775 (piR-775) predicts favorable prognosis and regulates cell cycle and DNA damage response pathways in breast cancer.
Article in Biomarker research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Minimally invasive circulating MicroRNA signatures for breast cancer detection and neoadjuvant therapy response prediction in a multicenter MENA cohort.Journal of translational medicine · 2026Article
- Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer.Current issues in molecular biology · 2026Review
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Authors and funding
8 authors.
Funding
Abstract
Piwi-interacting RNAs (piRNAs) are small non-coding RNAs primarily recognized for their roles in germline development and genome stability. However, their contribution to breast cancer remains poorly understood. In this study, we profiled piRNA expression in 96 primary breast cancer tissues and explored the prognostic and functional significance of piR-775. Higher expression of piR-775 was significantly associated with improved relapse-free survival, suggesting its potential as a favorable prognostic biomarker. Functional assays in triple-negative breast cancer (TNBC) models demonstrated that piR-775 overexpression significantly suppressed colony formation and three-dimensional tumor growth. Using an organ-on-chip platform, piR-775 overexpression also inhibited TNBC cell migration and invasion. Transcriptomic analyses following piR-775 re-expression identified multiple downregulated target genes involved in cell cycle progression and DNA damage repair pathways, including POLE, BARD1, TPX2, BIRC5, and XRCC2, which were further validated by RT-qPCR. Integration with CRISPR screen data highlighted 47 essential piR-775 targets required for TNBC survival. Additionally, DNA damage assays indicated increased genomic instability upon piR-775 expression. Notably, combining piR-775 with the PARP inhibitor Olaparib led to enhanced cytotoxic effects, suggesting a synthetic lethal interaction. Furthermore, transcriptomic analysis of breast cancer revealed consistent downregulation of the PIWI proteins PIWIL2 and PIWIL4, indicating disruption of the piRNA–PIWI pathway in breast cancer. Collectively, these findings establish piR-775 as a tumor-suppressive piRNA with both prognostic and therapeutic relevance in breast cancer, particularly in TNBC. By impairing oncogenic signaling and enhancing the efficacy of PARP inhibitors, piR-775 emerges as a promising biomarker and a candidate for combination therapy.
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