Study Of The Expression And Biological Functions Of Thioredoxin Interacting Protein(TXNIP)in Prostate Cancer

BackgroundProstate cancer(PCa)is one of the most commonly diagnosed cancers all over the world and it is a serious problem to men's health.Therefore,it is a hot spot to find a molecular target for the treatment of prostate cancer.Loss of thioredoxin interacting protein(TXNIP)expression has been detected in a great number of human tumors.However,it has not yet been deeply studied the specific biological functions of TXNIP on the development of prostate cancer.ObjectivesThe expression of TXNIP in prostate cancer tissues was studied,and the correlation between the expression level of TXNIP and clinicopathological parameters of prostate cancer was analyzed.To further explore the effects of upregulation of TXNIP on cells proliferation,cell cycle,apoptosis,migration and invasion,cell experiments was performed in vitro.To reveal the biological functions of TXNIP in the development of prostate cancer and provide experimental data basis for molecular therapy of prostate cancer.Methods1.PCa tissues were obtained from 50 patients(49 benign prostatic hyperplasia tissues as control group).Detect the expression level of TXNIP in prostatic tissues by immunohistochemical staining and analyze the correlation between the expression level of TXNIP and clinicopathological parameters.2.TXNIP were up-regulated in PC-3 cells by lentiviral transfection techniques.Divided the cells into three groups:blank control group(CON),negative control group(LV-NC)and TXNIP overexpression group(LV-TXNIP).Then verify the transfection efficiency by qRT-PCR and Western Blot.3.After stable cell transfection,CCK-8 and clone formation assay were used to detect the proliferation of PC-3 cells.Flow cytometry was used to detect PC-3 cell apoptosis and cell cycle distribution.Wound healing assay and Transwell Matrigel invasion were used to detect cell migration and invasion ability.Results1.The positive rate of TXNIP in PCa tissues was 36.0%(18/50),which was significantly lower than the positive rate in BPH tissues 79.6%(39/49),P<0.05.The positive expression rate of TXNIP in prostate cancer tissues was significantly correlated with prostate specific antigen(PSA),TNM stage and Gleason scores(P<0.05),but not age.2.After PC-3 cells was transfected by lentivirus,the puromycin was screened,followed by qRT-PCR and Western Blot.The results showed that in contrast with the blank control(CON)group and LV-NC group,the mRNA and protein levels of TXNIP in the LV-TXNIP group were markedly elevated(P<0.001).3.Compared with the CON group and the LV-NC group,the proliferation,colony formation abilities,invasion and migration abilities of PC-3 cells were significantly decreased in the LV-TXNIP group.In addition,overexpression of TXNIP in the LV-TXNIP group induced cell cycle arrest in G0/G1 phase and cell apoptosis(P<0.05).ConclusionLoss of TXNIP expression was detected in prostate cancer tissues and positive expression rate of TXNIP was significantly associated with PSA,TNM stage and Gleason scores.TXNIP may play a role in inhibiting the proliferation,invasion and migration abilities of prostate cancer PC-3 cells and promoting cell apoptosis and arresting at GO/1 phase.