Abstract
Our previous research demonstrated that TERT and concurrent PIK3CA mutations predict worse overall survival in patients with poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma. However, the molecular mechanism underlying the synergistic oncogenic operations of the two oncogenes is unclear. This study aimed to explore further the effect of TERT and PIK3CA co-mutation on the malignant biological phenotype of thyroid carcinoma and its possible mechanism. PIK3CA E545K mutation plasmid was transfected into thyroid anaplastic cancer cell line (C643) with TERT promoter mutation, then CCK-8 and transwell invasion assays were used to investigate the ability of cell proliferation and invasion, respectively. RT-qPCR and western blot were performed to detect the expression of PIK3CA, TERT, GABPA and GABPB1. GABPA/GABPB1 siRNA plasmid was transfected with C643 cells, then the ability of cell proliferation and invasion were identified. We also detected the expression of PIK3CA and TERT. C643 cells carry TERT promoter mutation C228T. Concurrent PIK3CA E545K and TERT mutation markedly enhanced the proliferation and invasion of C643 cell in vitro, with significantly increased mRNA/protein expression of PIK3CA, TERT, GABPA and GABPB1. Knocking down GABPA markedly inhibited cell proliferation. Knocking down of GABPB1 significantly decreased the proliferation and invasion of C643 cells, with much lower expression of PIK3CA and TERT. TERT and PIK3CA co-mutations promote the proliferation and invasion of thyroid anaplastic carcinoma cells and may be caused by up-regulating the expression of GABPA and GABPB1.
Keywords
Thyroid carcinoma, TERT, PIK3CA, Proliferation, Invasion, GABPA, GABPB1