The Role And Mechanism Of PDE12 In The Development Of Colon Cancer

In recent years,the mortality rate from colorectal cancer(CRC)has ranked fourth among malignancies worldwide,and the incidence is on the rise.The early onset of CRC is characterized by insidious and diverse symptoms,which makes a large number of patients in the advanced stage of diagnosis,miss the good opportunity for treatment,resulting in a poor prognosis.Therefore,it is urgent to explore new molecular targets to provide a more effective basis and strategy for the diagnosis and treatment of CRC.Studies have shown that phosphodiesterase 12(PDE12)is involved in important biological processes such as cell defense against virus,mitochondrial RNA maturation and repair,and mitochondrial oxidative phosphorylation.But it has not been reported in tumors,especially colon cancer.In this paper,for the first time,colon cancer in colorectal cancer is taken as the research object,and the important role and mechanism of PDE12 in the development of colon cancer are discussed in many aspects.The role of PDE12 as an oncogene was identified for the first time,which provided a scientific experimental basis for exploring new drug therapeutic targets and effective treatment regimens for colon cancer.This study found that the expression of PDE12 protein in colon cancer tissues was significantly higher than in para-carcinoma tissues and normal tissues,but there was no significant difference in expression in para-carcinoma tissues and normal tissues.The expression of PDE12 is related to the age,T stage and clinical grade of colon cancer patients,and it has good specificity and sensitivity for the identification of colon cancer.Knockdown of PDE12 inhibited colon cancer cell proliferation,colony formation and subcutaneous xenograft formation in nude mice.Knocking down PDE12 also caused a decrease in ECAR(extracellular acidification rate),OCR(oxygen consumption rate)and an increase in real-time ATP production rate in colon cancer cells.In addition,it promoted the apoptosis of colon cancer cells and the production of ROS(reactive oxygen species).Further studies have found that knocking down PDE12 significantly inhibited the phosphorylation of the transcription factor CREB(cAMP-response element binding protein)and ATF1(activating transcription factor 1),mediated the decrease of anti-apoptotic protein Bcl-2,and the increase of pro-apoptotic protein Caspase-3 and PARP.In summary,PDE12,which is highly expressed in colon cancer,is involved in the regulation of the development of colon cancer by promoting the cell growth,aerobic glycolysis and the anti-apoptosis.Moreover,PDE12 may regulate the anti-apoptotic activity of colon cancer cells mediated by the CREB signaling pathway.PDE12 may be a potential target for clinical diagnosis and gene therapy of colon cancer.