Novel dimensions of piRNAs in cancer

•Piwi-interacting RNAs (piRNAs) may direct the Piwi-dependent biological functions.•piRNAs are the most mysterious class of small regulatory RNAs in tumorigenesis.•piRNAs may be disregulated and play crucial roles in tumorigenesis.

Piwi-interacting RNAs (piRNAs), a newly identified class of small non-coding RNAs, direct the Piwi-dependent transposon silencing, heterochromatin modification and germ cell maintenance. Owing to our limited knowledge regarding their biogenesis, piRNAs are considered as the most mysterious class of small regulatory RNAs, particularly in pathogenesis such as tumorigenesis. Recently, several lines of evidence have emerged to suggest that piRNAs may be dis-regulated and play crucial roles in tumorigenesis in previously unsuspected ways. In this prospective piece, we will discuss the emerging insights into the potential novel roles of piRNAs in carcinogenesis and highlight their potential implications in cancer detection, classification and therapy.