Comprehensive landscape and future perspectives of PIWI‑interacting RNAs in cancer (Review).

Abstract

P‑element induced wimpy testis (PIWI)‑interacting RNAs (piRNAs) are small non‑coding RNAs with a length of ~24‑32 nucleotides that specifically bind members of the PIWI protein family. Initially identified in germ cells, piRNAs have since been detected in various somatic cells. They regulate multiple physiological and pathological processes and their aberrant expression contributes to human diseases, including cancer. Recent studies indicate that piRNAs influence key tumour behaviours‑including malignant proliferation, invasion and metastasis, angiogenesis, immune evasion and metabolic reprogramming‑through epigenetic, transcriptional and post‑transcriptional mechanisms. In tumour‑bearing mouse models, exogenous knockdown or overexpression of piRNAs using nanodelivery systems can markedly inhibit tumour growth, supporting their potential as therapeutic targets. piRNAs are also stably expressed in tumour tissues and bodily fluids, such as serum and urine, either freely circulating or encapsulated within extracellular vesicles; their dysregulation is associated with clinicopathological features of tumours. Accordingly, piRNAs may serve as novel pathological diagnostic markers or liquid biopsy biomarkers. This review summarises piRNA expression patterns and molecular mechanisms, evaluates their clinical potential in cancer diagnosis and treatment and integrates advances in high‑throughput sequencing and nanodelivery technologies to provide a theoretical basis and research foundation for the clinical translation of piRNA‑related studies.