MiR-1246: a new link of the p53 family with cancer and Down syndrome

Abstract

Since the discovery of miRNAs, a number of miRNAs have been identified as p53's transcriptional targets. Most of them are involved in regulation of the known p53 functions, such as cell cycle, apoptosis and senescence. Our recent study revealed miR-1246 as a novel target of p53 and its analogs p63 and p73 to suppress the expression of DYRK1A and consequently activate NFAT, both of which are associated with Down syndrome and possibly with tumorigenesis. This finding suggests that miR-1246 might serve as a likely link of the p53 family with Down syndrome. Here, we provide some prospective views on the potential role of the p53 family in Down syndrome via miR-1246 and propose a new p53-miR-1246-DYRK1A-NFAT pathway in cancer.

Figure 1. Summary of the p53 target miRNAs. Most p53 targeting miRNAs are involved in known p53 functions including cell cycle arrest, senescence, and apoptosis.

Figure 2. Screening of miR-1246 targets by western blot (WB). H1299 cells were harvested 72 h after transiently transfected with miR-1246 for Q-RT-PCR analysis of mature miR-1246 levels (A) and for WB with antibodies as indicated (B). Error bars represent standard deviation (n = 3)