P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are regulatory small non-coding RNAs that participate in transposon inactivation, chromatin regulation, and endogenous gene regulation. Numerous genetic and epigenetic factors regulate cell proliferation and tumor metastasis. PIWI proteins and piRNAs have been revealed to function in regulating upstream or downstream of oncogenes or tumor-suppressor genes in cancer tissues. In the present review, we summarize major recent findings in uncovering the regulation and role of PIWI proteins and piRNAs in tumorigenesis and highlight some of the promising applications of specific piRNAs in cancer therapeutics and as cancer biomarkers.
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