Piwi-interacting RNAs (piRNAs) and PIWI proteins are emerging key players in the regulation of cancer gene expression and tumor biology. piRNAs (24-31 nucleotides), interact with PIWI proteins to regulate gene expression via epigenetic mechanisms, modulating cell proliferation, apoptosis, and metastasis. Dysregulated piRNA-PIWI axis is implicated across cancer types - breast, colorectal, genitourinary, etc., and correlates with tumor progression and poor patient outcomes. Notably, piRNAs influence cancer stem cell maintenance, contributing to tumor aggressiveness and therapeutic resistance. We also highlight the significant diagnostic and prognostic potential of piRNAs (e.g. piRNA-823) due to their unique expression profiles in cancerous tissues potentially contributing to early detection and disease monitoring. Additionally, noninvasive detection of piRNAs in extracellular vesicles offers promise for liquid biopsy applications, enabling real-time monitoring of cancer progression and treatment response. On the therapeutic front, piRNA-PIWI protein axis offers innovative avenues - modulating piRNA expression or restoring normal PIWI function can limit tumor growth, metastasis, etc. Despite cumulative evidence supporting their role in cancer, challenges remain in translating piRNA research into clinical practice (lack of standardized protocols, effective therapeutic strategies). Ongoing studies into elucidating molecular implications of piRNA-PIWI axis are crucial for tapping this axis for diagnostic and therapeutic applications.
Sharma et al. (2026) studied this question.