The disease-related biological functions of PIWI-interacting RNAs (piRNAs) and underlying molecular mechanisms

More than a decade ago, PIWI-interacting RNA (piRNA) was discovered almost simultaneously by four different research groups. The length of this type of single stranded noncoding RNA is 24~31 nucleotides (nt), with most of the piRNAs fall into the range of 29~30 nt. PiRNAs form specific RNA-induced silencing complex with PIWI subfamily proteins, which is how piRNA got its name. PiRNAs are initially famous for the crucial roles they played in germline cells. Binding with PIWI family proteins, piRNAs is able to affect methylation of genomic DNA in germline cells and, therefore, maintaining genomic stability and suppressing transposons. Since mammalian PIWI subfamily proteins are mainly germline specific, it was once thought that piRNAs might only function in the gonadal cells. However, evidence from the later research suggest that piRNAs are broadly expressed in many kinds of somatic cells and are involved in numerous pathological condition far beyond those have been reported in the germline. For example, piRNAs were discovered to be abnormally expressed in several kinds of cancers. PiRNAs are also shown to be promising prognostic markers for various types of cancers. Interestingly, a recent research indicated that piRNAs are also regulators for pancreatic beta cell function. PiRNAs are promising regulators for the development of type 2 diabetes. From a disease-oriented point of view, this review will focus on both confirmed and proposed biological functions of piRNAs mostly in those fields beyond germline cells. Meanwhile, some of the underlying molecular mechanisms will also be mentioned.