miR-144/451 Promote Cell Proliferation via Targeting PTEN/AKT Pathway in Insulinomas

Insulinoma is the main type of functional pancreatic neuroendocrine tumors. The functional microRNAs ( miRNAs) regulating tumor growth and progression in insulinomas are still unknown. We conducted the miRNA expression profile analysis using miRNA quantitative RT-PCR array and identified 114 differentially expressed miRNAs in human insulinomas compared with normal pancreatic islets. Forty-one differentially expressed miRNAs belonged to 7 miRNA families, and 28 miRNAs in 3 of the families localized in the epigenetically regulated imprinted chromosome 14q32 region. We validated the most significant differentially expressed miRNA cluster miR-144/451 in another 8 human normal islet samples and 25 insulinomas. Our data showed that the overexpression of miR-144/451 in mouse pancreatic beta-cells promoted cell proliferation by targeting the beta-cell regulator phosphatase and tensin homolog deleted on chromosome ten/v-akt murine thymoma viral on cogene homolog pathway and cyclin-dependent kinase inhibitor 2D. Our findings highlight the importance of functional miRNAs in insulinomas.