Effect Of Pgk1 On Radiosensitivity Through Regulation Of Cin And Cfl1 In Human Glioma Cells.
JOURNAL OF CLINICAL ONCOLOGY(2019)
摘要
e14631 Background: Phosphoglycerate kinase 1 (PGK1) has been detected overexpressed in many malignancies and usually correlated with increased tumorigenesis and poor survival. Our previous study revealed that PGK1 significantly up-regulated and positively correlated with cofilin-1 (CFL1) expression in radioresistant astrocytomas samples. However, the further mechanism remains unknown. Methods: In the present study, functional interactions among PGK1, chronophin (CIN) and CFL1 were analyzed by co-immunoprecipitation and immunofluorescence experiments. Transfection of shRNA and pcDNA3.1-plasmid were respectively utilized to silence and overexpress PGK1 or CIN in both normal glioma cells (U251 and U373) and estabilshed radioresistant (RR-U251 and RR-U373) cells. The effect of PGK1 on CIN and CFL1 expression levels was investigated with Western-blot method; while the effect of PGK1 or CIN on radiosensitivity of glioma cells was evaluated using cell viability, migration and invasion assays after irradiation. Results: Cell proliferation, migration and invasion abilities significantly increased in RR-U251 and RR-U373 cells compared with those of normal cells, indicating the successful establishment of RR-glioma cell models. Laser confocal experiment in vitro showed the colocalization of PGK1 and CIN. Meanwhile, PGK1 specifically and directly combined with CIN, while did not interplay with CFL1. Elevated PGK1 expression level was observed in radioresistant cells compared with that of normal cells. The western blot analysis showed that CFL1 and CIN levels were positively correlated with the PGK1 expression in both normal and radioresistant cells. The proliferation, migration and invasion capabilities significantly decreased in PGK1-silenced and CIN-silenced glioma cells, indicating the improvement of the radiosensitivity of radioresistant cells. Conclusions: Our research implied the effect of CIN-mediated PGK1 regulation on CFL1 level, thereby altering the migration and invasion abilities in nomal and notably radioresistant glioma cells. These findings clarify a novel underlying mechanism of radioresistance in glioma cells and provide valid basis for further explorations concerning radiotherapy.
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