Effects of Novel ncRNA Molecules, p15-piRNAs, on the Methylation of DNA and Histone H3 of the CDKN2B Promoter Region in U937 Cells.

ABSTRACT

Non-coding RNAs (ncRNAs) play key roles in epigenetic events. However, the exact mechanism of ncRNA guidance, particularly piwi-interacting RNAs (piRNAs), for the targeting of epigenetic regulatory factors to specific gene regions is unclear. Although piRNA function was first established in germ-line cells, piRNA may be crucial in cancer cells. This study investigated the potential roles of CDKN2B-related piRNA in leukemia cells to provide a potential tumorigenesis model of leukemia. CDKN2B-related piRNAs, hsa_piR_014637 and hsa_piR_011186 were transduced into the leukemia cell line U937 to study the effect of these two piRNAs on cell-cycle progression, apoptosis, heterochromatin formation, CDKN2B methylation and expression. Our results show that over-expressing hsa_piR_011186 promoted cell-cycle progression and decreased apoptosis. We also observed inhibition of CDKN2B gene expression. These effects were likely mediated by novel piRC (piRNA complex) of CDKN2B-related piRNA that associate with DNMT1, Suv39H1 and/or EZH2 proteins to modulate the methylation of DNA and histone H3 in the promoter region of the CDKN2B gene. The novel piRC complex facilitated epigenetic modifications on the promoter of cell-cycle regulating genes, providing an expanded view of the role of piRNA in the progression of leukemia cells.