A Study on the Role of piRNAs in Cancer Epigenetics

Piwi-interacting RNAs (piRNAs) are single-stranded, small noncoding RNAs that are 24–30 nucleotides long and have a 5′-U end and a 2′-O-methylation at the 3′ end. piRNAs associate with Piwi proteins that cleave them then enters the nucleus to induce epigenetic modification, transcriptional and post-transcriptional gene silencing. The piRNA and PIWI proteins mediate various epigenetic changes, such as DNA methylation, histone modification via methylation, gene regulation via transposon silencing, and chromatin remodelling. Various DNA methyltransferases, such as DNMT1, DNMT3A, and DNMT3B, catalyse the cytosine methylation of DNA molecules. Histone methylation on lysine and arginine residues of H3 and H4 histone proteins is done by various methyl transferases. Suv39H1 and SETDB1 methyltransferase enzymes are involved in lysine methylation on histone H3 and H4, and the protein arginine methyltransferase-5 (PRMT-5) enzyme causes the methylation of arginine residues on histone H3. Upregulation and downregulation of Piwi proteins and piRNAs may have the ability to suppress cancer growth and metastasis. Various studies have shown that piRNA-mediated modifications can be used as biomarkers for the diagnosis, prognosis of various diseases, such as different types of human malignancies, type-II diabetes mellitus, and Alzheimer’s disease. In this chapter, the current findings and functions of piRNAs in cancer epigenetics are discussed.