The Role Of FKBP10 In Gastric Cancer Progression

Gastric cancer is one of the most common malignant cancer in the world.In China,the incidence of gastric cancer ranks second in malignant tumors.Most patients being diagnosed have already been in the advanced stage of gastric cancer,with only 5%of the five-year survival rate.Metastasis is an essential factor affecting the prognosis and survival of those patients.At present,the clinical diagnosis and treatment based on pathological staging is still far away from curable for advanced gastric cancer patients.Therefore,it is important to figure out the underlying mechanism of gastric cancer progression and metastasis.It is theoretically and clinically significant to find specific molecular markers for gastric cancer diagnosis and treatment.FKBP10(FK506 binding protein 10,also known as FKBP65)exists in the endoplasmic reticulum cavity.It is reported that FKBP10 has PPIase activity which can help Tropoelastin and Collagen forming correct conformations and secreting to the extracellular matrix.Previous studies show that FKBP10 is highly expressed in ovarian cancer and colorectal cancer,but its molecular mechanism and biological function are largely unknown.In this study,we analyzed FKBP10 mRNA level in gastric cancer tissue samples using RNA-seq data from publicly available database TCGA.FKBP10 was highly expressed in cancer tissues than in corresponding adjacent normal tissues.We further detected FKBP10 mRNA and protein expression in our collected gastric cancer tissues,showing that FKBP10 was significantly higher in cancer tissues.It indicates that FKBP10 may be an essential gene regulating the development of gastric cancer.To elucidate the biological function of FKBP10 gastric cancer,RNAi experiment was performed in gastric cancer cell lines.Our data show that FKBP10 knockdown has no effect on cell proliferation and cell cycle.However,knockdown of FK1BP10 not only significantly promotes cell migration and invasion,but also inhibits cell adhesion.In addition,overexpressing FKBP10 has no influence on cell proliferation and cell cycle,but can promote cell adhesion.To validate the phenotype caused by FKBP10 knockdown,we constructed FKBPIO mutated cell lines by CRISPR/Cas9,and found that cell proliferation and cell cycle is not affected.In addition,cell migration and invasion ability are significantly enhanced in FKBPIO mutated cell lines,being consisitent with phenotypes detected in RNA interference experiments.Furthermore,to determine the role of FKBP10 in gastric cancer metastasis,we used nude mouse as animal model.Wildtype and FKBPIO mutant cell lines were injected into nude mice tail vein to investigate their capability of lung metasatasis.The data show that knockout of FKBP10 greatly promotes lung metastasis,indicating that FKBP10 may be involved in regulating gastric cancer metastasis.In conclusion,we find that FKBP10 is highly expressed in gastric cancer tissues and significantly associated with prognosis of gastric cancer patients.It is involved in the regulation of gastric cancer cell migration,invasion and adhesion,thus affecting gastric cancer metastasis.This study contributes to elucidate the functional role of FKBP10 in regulating progression of gastric cancer,and provides the evidence that FKBP10 may be a new potential therapeutic target for clinical diagnosis and treatment of gastric cancer.