Study the Function and Regulation of miRNAs in Pancreatic Cancer Progression (I)

Pancreatic cancer is a common malignancy with the poor prognosis in the world. It is the fourth leading cause of cancer-related deaths in the United States and the eighth leading cause of death from cancer in the Taiwan. Due to lack of symptoms and limitation in diagnostic methods, patients are mostly diagnosed at advanced stages. Therefore, more understanding of the carcinogenetic mechanisms of pancreatic cancer may provide more potential diagnostic and therapeutic strategy. Recently, many evidence has indicated that small subset of cells within a tumor support tumor growth and metastasis, which are cancer stem cells. It has been suggested that pancreatic cancer stem cell (panCSC) is involved in the role of tumor progression, metastasis and chemoresistance. Thus, it is timely to investigate the molecular mechanisms of cancer stem cell development. It has been reported that microRNAs (miRNAs) are involved in cancer progression. Emerging evidence has revealed that miRNAs play critical role in the regulation of cancer stem cells. Therefore, alternative expression of miRNA profile may contribute to tumor initiation and progression. In recent years, secreted miRNAs has been suggested as a new form of cell-cell communication. It has been reported that secreted miRNAs play a role in the communication between cancer cells and their stromal cells. For this reason, our plan will focus on the potential implication of aberrant miRNAs expression in pancreatic cancer. The specific aims as following will help us to reveal the goal. Specific Aim 1: Study the role of critical miRNA in pancreatic cancer progression. Specific Aim 2: Identify the downstream targets of candidate miRNAs in pancreatic cancer progression. Specific Aim 3: Study the epigenetic and molecular mechanisms involving in the regulation of candidate miRNAs. Specific Aim 4: Investigate the physiological significance of candidate miRNAs in animal model and pancreatic cancer patients. Achievements of these specific aims will help us to understand better about functions and molecular mechanism of miRNA in pancreatic cancer progression. Furthermore, the findings from this project may provide more diagnostic and therapeutic targets in developing anti-pancreatic cancer pharmaceuticals.