MiR-18a, MiR-145 And MiR-495 Repress Ptf1a Expression In Developing Mouse Pancreas

Pancreas is a mixed organ with endocrine and exocrine cells. Absence or dysfunction ofβcells in endocrine pancreas would lead to diabetes, and abnormal proliferation of exocrine cells would cause pancreatic cancer, so the mechanism of pancreatic development is of great significance for treating pancreatic disease. Ptfla, a bHLH transcription factor, is an essential transcriptional factor involved in pancreas specification and exocrine development. A recent research showed Ptfla is required for regulating pancreatic endocrine and exocrine fates in a dose-dependent manner: low levels of Ptfla promote endocrine fate, whereas high levels of Ptfla repress endocrine fate and promote exocrine fate. However, it is unclear about the mechanism regulating the expression of Ptfla in pancreatic cells with different developmental fate.MicroRNAs (miRNAs) are a class of approximately 22-nucleotide non-coding RNAs which are highly conserved, and they regulate the expression of genes targeting mRNAs for cleavage or translational repression. Although some miRNAs have been identified playing essential roles in mouse pancreas development and functional regulation, it is still unknown which miRNAs can regulate the expression of Ptfla in developing pancreatic epithelium.To address this question, we first predicted miRNAs which could regulate the expression of Ptfla by integrating results of two prediction algorithms. Among these miRNAs, miR-18, miR-145 and miR-495 are established to be the real regulators of Ptfla by dual luciferace reporter assays. The expression patterns of miR-18a and Ptfla mRNA showed negative correlations in developing mouse pancreas by qRT-PCR assays, and did that of miR-145/miR495 and Ptfla protein by immunofluorescence staining. Finally, to further comprehend the Ptfla related molecular mechanisms in developing mouse pancreas, we mapped a Ptfla related regulatory pathway by coordinating previous published data and the results in this study.Overall, these results indicate that miR-18a, miR-145 and miR-495 can repress Ptfla expression and participate in a Ptfla related regulatory pathway during pancreatic development in mouse.