Ali Nakhaei, Arezoo Omidkhoda, Farzaneh Abbasinezhad-Moud, Elaheh Gheybi, Farzaneh Davoudi, Mohammad Jalili-Nik, Ali Gorji
Non-coding RNAs serve as key regulators of gene expression at both the transcriptional and post-transcriptional levels. Among them, piRNAs, a class of small non-coding RNAs, have emerged as significant mediators in cancer biology. PIWI proteins, members of the Argonaute family highly expressed in germline cells, interact with piRNAs to form piRNA/PIWI complexes, which play a key role in the development, recurrence, and metastasis of several malignancies, including gliomas. This review describes the biological functions of PIWI proteins and piRNAs, emphasizing their roles in cancer-related processes such as proliferation, migration, invasion, cell cycle regulation, epigenetic modification, immunity, DNA damage, and aging. Moreover, the clinical promise of piRNAs as biomarkers and therapeutic agents is discussed, with particular focus on glioblastoma, an area of growing research interest.