The Role Of MicroRNA-103 Targeted PDCD10 In Prostate Cancer And The Underlying Molecular Mechanism

Backgroud and Purpose:Prostate cancer severely affects men's health worldwide representing the second leading cancer in men and the incidence rate is increasing rapidly in aging male.Prostate cancer is difficult to cure with high mortality seriously threatening public health.Therefore,it is of great importance to develop novel targets and therapeutic approaches for preventing and treating prostate cancer according to the molecular pathogenesis underlying the development and progression of prostate cancer.Recent studies have suggested that the pathogenesis of prostate cancer includes androgenic hormone dependent prostate cancer and primary and secondary hormone independent prostate cancer and indicated that androgenic hormone dependent prostate cancer plays an important role in the development and progression of prostate cancer.Recent study reports that miR-103 mediated programmed cell death factor 10(PDCD10)plays a critical role in the development and progression of prostate cancer contributing to the pathogenesis of prostate cancer.PDCD10 can regulate cell aoptosis in the body which plays an important role in the maintaining cell survival of the body.The dysregulation of PDCD10 in prostate cells will induce prostate lesions even leading to the pathogenesis of prostate cancer.PDCD10 is abundantly expressed in human cells and is involved in various physiological and pathological processes.To date,PDCD10 has been found to play an important role in numerous cancer types.In addition,miR-103 has been found in varous cancer cells including colorectal cancer and plays an impotant role in the regulation of development and cancer progression.miRNAs exert oncogenic or tumor suppressive roles by regulating the expression of cancer-related genes.Recent studies found that mi R-103 regulates gene expression through targeting the noncoding region of target genes which is involved in the pathogenesis of cancer.Overall,miR-103 mediated PDCD10 in prosate cells is closely associated with the development and progression of prostate cancer.However,the relationship between mi R-103/PDCD10 and prostate cancer and the regulation pattern of miR-103/PDCD10 remain unknown.Therefore,the associated scientific problems need further study.This study aimed to investigate the expression change of miR-103 and PDCD10 in prosate cancer cells of prosate cancer patients.Based on the expression pattern of mi R-103 and PDCD10,this study elucidates the role of miR-103 and PDCD10 in the pathogenesis of prostate cancer which will provide novel insights into understanding the molecular pathogenesis of prostate cancer and provide novel targets and theoretical basis for prevention and treatment of prostate cancer.Methods:1.The expression pattern of miR-103 in prostate cancer tissues and cell lines was detected by Real-time PCR.2.The expression of PDCD10 in prostate cancer tissues and cell lines was detected by Western blotting and Real-time PCR.3.The effect of miR-103 and PDCD10 on prostate cancer cell proliferation,apoptosis and cell cyle was detected by MTT,flow cytometry,cell counting and cell transfection assays.The interaction of mi R-103 between PDCD10 and MST4 was detected by yeast two hybrid experiments.The effect of mi R-103 on the phosphorylation of ERK protein was examined by Western blotting and Real-time PCR.Results:1.The expression of miR-103 was significantly decreased in prostate cancer tissues and cell lines as compared with normal controls.2.In vitro experiments showed that mi R-103 inhibited prostate cancer cell proliferation and invasion and promoted cell apoptosis of prostate cancer cells.Furhtermore,overexpression of miR-103 suppressed cell cycle transition from G1 phase to S phase.3.The expression of PDCD10 was highly expressed in prostate cancer tissues and cell lines compared with normal controls.4.In vitro experiments showed that PDCD10 inhibited prostate cancer cell apoptosis and promoted cell proliferation and invasion of prostate cancer cells.In prostate cancer cells,PDCD10 could interact with MST4 protein and express synergistically.Overexpression of PDCD10 promoted the phosphorylation of ERK protein and protected prostate cancer cells against oxdative stress induced cell injury.5.The expression nof PDCD10 was directly regulated by miR-103.Overexpression of miR-103 inhibited PDCD10 expression in prostate cancer cells leading to decreased expression of MST4 protein and phosphorylation of ERK protein which redued the antioxidative stress ablity of prostate cancer cells.Conclusions:1.The expression of miR-103 was decreased while PDCD10 was increased in prostate cancer cells which contributed the increased cell proliferation and decreased cell apoptosis of prostate cancer cells.2.miR-103 inhibited cell proliferation,invasion and cell cycle transition from G1 phase to S phase through directly downregulation of PDCD10 expression.3.miR-103 inhibited MST4 protein expression and phosphorylation of ERK by downregulation of PDCD10 which induced a decrease in antioxidative stress ablity of prostate cancer cells.4.miR-103 inhibited the development and progression of prostate cancer by targeting PDCD10,provding novel theoretical basis and new targets for treatment of prostate cancer.