MicroR-18a Regulates Expression Of The Pancreatic Transcription Factor Ptf1a In Pancreatic Progenitor And Acinar Cells

The pancreas is the second largest gland organ only after liver. The mixed gland consists of both endocrine and exocrine, maintaining blood glucose metabolism and functioning physiological progress of food digestion. Pancreas specific transcription factor Ptfla plays an important role in the entire development process, Ptf1a appearing in the naive epithelial cells during early development period, regulates cell growth and proliferation; low level of Ptf1a promotes endocrine fate, whereas high of Ptfla expression level represses endocrine fate and promote exocrine fate. In the mature acinar cells, Ptf1a expression level is extremely high, and Ptf1a could bind promoter of the digestive enzyme genes to regulate digestive enzymes. Now, molecular regulation mechanism research of the pancreas and related disease is not yet clear, especially the regulation of Ptf1a, therefore to explore molecular mechanism of the pancreas has profound significance.MicroRNAs (miRNAs) is the biological research hotspot, the class of short (about22-25nt) and encoding RNA plays a crucial role in the process of development, metabolic, disease cancerous tumors in post transcription regulation level. MiR-18a, which highly expressed in many organs is the member of MiR-17-92family, play an important role in regulating the cell proliferation, differentiation and other physiological processes. Research through the quantitative RT-PCR analysis the expression mode of miR-18a and Ptfla in the development of the pancreas and the pancreatic cells, which confirms miR-18a targets Ptfla, and explores the regulation effects of the pancreas when overexpressing miR-18a in pancreatic progenitor cells and acinar cells.The result shows the expression levels of miR-18a are the highest at e12.5, and the lowest at e18.5, the Ptfla expression mode is opposite to miR-18a in the process; In the pancreatic cell lines, the expression levels of miR-18a are the highest in the progenitor cells, and the lowest in MIN6, and the expression of Ptfla is the highest in AR42J cells but doesn’t express in MIN6; In3T3cell lines miR-18represses both mRNA and protein of Ptf1a, dual luciferase reporter system analysis show that Ptfla is a direct target gene of miR-18a from the positive and the negative sides; In the pancreatic progenitor cells MiR-18fine tuning regulates the endogenous and exogenous Ptf1a, and has the weak effect on the total cell count, the morphology of progenitor cells, and genes expression; In AR42J cells the overexpression of MiR-18could repress Ptf1a protein expression, and then inhibit the endocrine enzymes gene transcription.To sum up, Ptf1a is regulated by miR-18a both in pancreatic progenitor cells and acinar cells, which influences the downstream related gene expression, though miR-18a only exerts a fine-tuning regulation of Ptf1a expression in pancreatic progenitor cells and acinar cells, these results will lay the foundation for the further research of pancreas and the related diseases.