Inactivation of PHLDA3 gene leading to tumorigenesis of pancreatic neuroendocrine tumors and its molecular mechanisms

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Introduction: The molecular mechanism underlying the tumorigenesis of sporadic pancreatic neuroendocrine tumors (PNETs) is largely unknown. Our previous studies showed that loss of heterozygosity (LOH) at chromosome 1q31 (including PHLDA3 gene) was frequently found in sporadic PNETs (2005 insulinoma and 2003 gastrinoma, respectively).

Aim(s): To confirm the role of PHLDA3 gene in the tumorigenesis of PNETs.

Materials and methods: We detected the expression of PHLDA3 protein in a large cohort of patients with PNETs by immunohistochemistry. The methylation status of PHLDA3 gene promoter is determined by methylation specific PCR. Microsatellite markers are used to detect the presence of PHLDA3 LOH. We knocked out PHLDA3 gene in rats by CRISPR-Cas9. The proliferation and apoptosis were detected by the MTT assay and flow cytometry in two PNETs cell lines with overexpression of PHLDA3. Phosphorylation of FOXO1 gene was detected by western blot.

Conference:

Presenting Author: Song Y

Authors: Song Y, Tong W, Wang Z, Chen Y,

Keywords: pancreatic neuroendocrine tumor, PHLDA3, tumorigenesis, prognosis,