Effects Of Down-regulation Of Phosphodiesterase 12 On Proliferation,migration And Invasion Of Gastric Cancer

Gastric cancer is currently the fifth most common type of cancer worldwide and the third leading cause of cancer death.Although the incidence of gastric cancer has gradually declined in the past few decades,gastric cancer is still a serious disease that harms human health.Gastric cancer often reaches the end stage when it is diagnosed clinically,so the timing of the best treatment is often missed.At present,the main treatment for gastric cancer patients is surgical treatment,but the overall five-year survival rate after treatment is not high.Therefore,it is urgent to find new molecular targets related to the pathogenesis of gastric cancer.Objective : Observe the role of PDE12 in the occurrence and development of gastric cancer,clarify the impact of PDE12 on the growth,proliferation,migration and invasion of gastric cancer cells and explore its possible mechanisms,as well as the possibility of PDE12 as a marker and treatment target for gastric cancer.Methods:Immune histochemical method(IHC)to verify the expression of PDE12 in gastric cancer and normal tissues Statistical analysis of clinical indicators.Further,by stabilizing the expression of PDE12,a stable and low-expressing gastric cancer cell line sh PDE12 was constructed,and then the growth of gastric cancer cells was investigated by the downregulation of PDE12 by cell proliferation toxicity test,Transwell experiment,scratch experiment,cell colony formation experiment,Ed U cell proliferation experiment The impact of migration,invasion and proliferation ability.The experimental data was analyzed using SPSS13.0 or Graphpad Prism statistical software,and the t-test for homogeneity of variance and t ’test for heterogeneous variance were used to compare statistical differences between groups.The experimental result is indicated by P <0.05 as the difference is statistically significant,and P <0.01 is indicated as the difference is statistically significant.Results:This study found that the proportion of PDE12 high expression in gastric cancer tissues(77.66%)was significantly higher than that in paracancerous tissues(12.79%)(P <0.0001),showing a high expression of tumor tissues.This phenomenon was also found in gastric cancer cells.The strain was verified by western blot experiment.Based on this,we subsequently transfected the sh PDE12 stable expression group with low expression of PDE12 and compared it with the non-silent p LKO.1 group of the control group.We found that the down-regulation of PDE12 expression significantly inhibited the growth rate of gastric cancer cells.The second day of culturing the HGC-27 cell line and the third day of the AGS cell line.The Ed U cell proliferation experiment found that the relative proliferation rate of the experimental group decreased by 26.97 ± 4.627(**,P <0.01).At the same time,we compared the colony formation ability of the two groups and found that the sh PDE12 group had a higher colony formation rate than the control group.Reduced by 18.9 ± 3.0% and 20.1 ± 4.2%(**,P <0.01).The Transwell experiment verified the migration and invasion ability of gastric cancer cells and found that the relative migration rate of the experimental group decreased by 65.90 ± 2.219(**,P<0.01),and the relative invasion rate decreased by 52.70 ± 2.364(**,P <0.01).In addition,the cell scratch test also showed the lower migration efficiency of the experimental group,indicating that the down-regulation of PDE12 expression had a significant inhibitory effect on cell proliferation,migration and invasion.Conclusion:The expression of PDE12 in gastric cancer tissues is higher than that of its corresponding paracancerous tissues,and the expression in gastric cancer cells is also significantly higher than that of normal gastric mucosa cells;PDE12down-regulation can significantly inhibit the growth and proliferation of gastric cancer cells in vitro;The ability of gastric cancer cells to migrate and invade in vitro.The above indicates that PDE12 plays an important role in the occurrence and development of gastric cancer,and provides a scientific basis for further clarifying whether PDE12 is used as a diagnostic marker and therapeutic target for gastric cancer.