microRNA-1225 inhibit apoptosis of pancreatic cancer cells via targeting JAK1.

The microRNA miRNA-1225-5p (miR-1225) is known as an essential modulator of the development of multiple cancers and other biological reactions. However, the understanding of its contribution to pancreatic cancer (PC) is insufficient. The effects of miR-1225 on PC cell survival and tumorigenesis in vivo as well as on the modulation of cell apoptosis were investigated. The expression of miR-1225 was upregulated in 20 human LC samples from acute myeloid leukemia patients with adverse prognosis and poor responses to therapy as well as in several human PC cell lines, as compared to that in healthy tissues, normal tissues, and normal pancreatic cells. In contrast, Janus kinase 1 (JAK1) expression was downregulated in human-derived PC samples and PC cell lines. EdU staining demonstrated that the aberrant expression of miR-1225 impaired the proliferation and survival of these two PC cell lines. The depletion of miR-1225 expression increased the apoptosis of both PANC-1 and AsPC-1 cells, as revealed by the TdT-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry results. The results of dual-luciferase reporter assay indicated that miR-1225 targeted the 3'-untranslated region of JAK1 for silencing. Silencing of JAK1 expression counteracted the suppressive influence of miR-1225 depletion in PC cells. Thus, these results offer an insight into the biological and molecular mechanisms underlying the development of PC and provide potential strategies for PC treatment.