**3. Conclusion and perspectives**

PiRNAs and PIWI proteins were first recognized more than a decade ago and are coming into attention with development of high-throughput sequencing technologies and bioinformatics methods. This pathway is considered as a conserved immune-like surveillance process to suppress propagation of TEs in germline cells and various types of somatic mostly nonaging cells. Furthermore, the PIWI-piRNA pathway seems to be implicated in maintain of the genome organization, epigenetic modifications of genes expression, and identification of self and nonself genes that are trans-generationally inherited. Moreover, this axis could be implicated in dual DNA/RNA-level regulation of genes expression. Nevertheless, there is still lack of complete understanding of the functions and interactions of piRNAs and PIWI proteins. Therefore, the complicated biogenesis and functions of piRNAs need further elucidation to improve our understanding of the implication of these molecules in cancer. Since discovery of the unexpected role of this pathway in seminoma, aberrant levels of expression of these molecules have been observed across numerous malignant tumors, though further research is needed to elucidate their oncogenic or tumor-suppressing status. Growing evidence suggests that the PIWI-piRNA pathway modulates occurrence of most of cancer hallmarks. PIWI proteins and piRNAs could be pertinent diagnostic/prognostic biomarkers in cancer and therapeutic tools in targeted therapies. However, the potential driver role of a deregulated PIWI-piRNA pathway in cancer needs to be further evaluated. Furthermore, it remains unclear whether PIWI proteins regulate cancer cell proliferation, apoptosis, metastasis, and invasion in the cytoplasm independently or PIWI proteins perform epigenetic control of homeostasis by taken to the nucleus with piRNAs. Most importantly, since the aberrant expression of this pathway may induce stemness, analysis of relationship between PIWI proteins, piRNAs, and cancer stem cells may open new avenues in future investigations.
