PinX1 Inhibits Telomerase Activity in Gastric Cancer Cells Through Mad1/c-Myc Pathway

The aim of this study was to investigate the role of Mad1/c-Myc in telomerase regulation in gastric cancer cells in order to gain insight into telomerase activity and to evaluate PinX1 as a putative inhibitor of gastric cancer. PinX1 and PinX1siRNA eukaryotic expression vectors were constructed by recombinant technology and transfected into gastric carcinoma cells using Lipofectamine (TM) 2000. Telomerase activity was measured by the telomeric repeat amplification protocol. Apoptosis of gastric cancer cells was analyzed by flow cytometry and transmission electron microscopy. Reverse transcription-polymerase chain reaction and Western blotting were used to assess the expression levels of PinX1 and Mad1/c-Myc. We found that PinX1-negative gastric cancer cells showed significantly higher telomerase activity than did the PinX1-postive cells. PinX1-transfection reduced telomerase activity in PinX1-negative gastric cancer cells and exhibited an upregulation of Mad1 and downregulation of c-Myc expression. Pinx1 RNAi treatment led to downregulation of Mad1 and upregulation of c-Myc. Suppression of telomerase activity mediated by PinX1 is involved in the Mad1/c-Myc pathway.