A Research About The Changes Of Circulating MiRNAs Expression In Prostate Cancer And The Anti-tumor Mechanism Of MiR-7 In Prostate Cancer

Objective To explore the changes of circulating miRNAs expression in prostate cancer and the anti-tumor mechanism of miR-7 in prostate cancer.Methods Blood serum of 53 new prostate cancer and 40 healthy controls of our hospital were to be screened for differently expressed miRNAs by TLDA,which were later verified by TaqMan prob method RT-qPCR,ROC was used to evaluate the diagnostic value of miRNAs to prostate cancer.24 pairs of FFPE samples of prostate cancer tissue and peritumoral lesion controls,through RNA extracting and RT-qPCR,the relative expression difference of miR-7 was studied to analyze its correlation with prostate cancer in clinicopathologic features.The effect of miR-7 to prostate cancer cells DU 145 in its activity,migration,invasiveness and apoptosis was studied by transient transfection to overexpress miR-7,bioinformatics were used to predict miR-7 target genes,which were later identified by dual luciferase experiment.Target genes were verified by RT-PCR in gene level,and Western-Blot in protein level.Results TLDA screened out 117 miRNAs which differently expressed over 3 multiples,among the serum of prostate cancer group,expression of 114 miRNAs up-regulated,3 down-regulated.It has been verified to have statistically significant difference between the expression of miR-378?miR-215?miR-206?miR-155 compared to healthy controls(P<0.01),same as to miR-203?miR-122?miR-7?miR-579 compared to healthy controls(P<0.05).According to ROC,AUC of miR-7,miR-122,miR-155,miR-203,miR-206,miR-215,miR-378,miR-579 were 0.689,0.645,0.733,0.651,0.713,0.683,0.707,0.660 individually.These 8 miRNAs could justly distinguish prostate cancer patients and healthy ones,which is of certain value in diagnosing prostate cancer clinically.Significantly down-expression of miR-7 was detected within prostate cancer tissue and peritumoral tissue.There are significant association between the relative expression quantity of miR-7 in prostate cancer tissue and Gleason scale based on the clinicopathologic features of prostate cancer patients.After overexpressing miR-7,prostate cancer cells DU 145 were distinctly inhibited in proliferation,its capacity to migrate and invade was weakend obviously,and the proportion of apoptotic cells apparently rised.Dual-luciferase report gene suggested EGFR to be the effect target of miR-7,overexpressed miR-7 inhibits the expression of EGFR gene and its protein.Conclusion miRNAs change characteristically in the blood circulation of prostate cancer patients compared to normal population as mostly up-regulating expression and a fraction of down-regulating expression,which could be applied in distinguishing prostate cancer patients and normal population,and it showed certain value in clinically diagnose prostate cancer patients.Expression of miR-7 in prostate cancer tissue down-regulated significantly compared to prostatic peritumoral tissue,which agreed with serum and its expression level is correlated to Gleason scale.miR-7 could regulate the expression of its target gene EGFR,and promote cellular early apoptosis,inhibit the proliferation,migration,invasiveness of prostate cancer cells DU145.