Mechanism Of MiRNA Let-7a In Regulating Invasion And Metastasis Of Prostate Cancer Cells By CCR7

objective:To explore the effect of miRNA let-7a on the invasion and metastasis of prostate cancer cells by regulating CCR7.Methods:Luciferase assays verify that let-7a regulates CCR7 via 3'UTR;Prostate cancer PC-3 cells were transfected with let-7a mimics and inhibitors respectively for 48 hours.Western blot detected the expressions of CCR7,ERK,P38,MMP-9 and EMT related proteins(E-cadherin protein,Snail protein and N-cadherin Protein);PC-3 cells were transfected with Let-7a inhibitor,and then added CCR7 siRNA for 48 hours,Western blot detected the expressions of ERK,P38 protein;P38,Erk inhibitor(SB233850,PD98059)were added into transfected Let-7a mimics of PC-3 cells cultured for 48 hours,Western blot detection E-cadherin protein,Snail protein and N-cadherin protein expression;Transwell was used to detect the invasion and metastasis of PC-3 cells after transfection.Results:Synthetic let-7a mimics decreased prostate cancer cell migration and invasion,as well as the expression of CCR7,phospho-p38,phospho-ERK1/2,MMP-9,N-cadherin and Snail in PC-3 cells.The let-7a inhibitors reversed the effects of let-7a on PC-3 cells.The 3'UTR of CCR7 was confirmed as a direct target of let-7a by using the luciferase assay.Western-blot results showed that Snail protein and N-cadherin protein expression decreased and E-cadherin protein expression increased after PC-3 cells transfected with Let-7a mimics followed by P38 and Erk inhibitor,Transwell experiments showed that prostate cancer PC-3 cells transfected with let-7a mimics,the invasion and metastasis decreased.Conclusions:All findings demonstrated that MiRNA let-7a can inhibit the invasion and metastasis of prostate cancer and epithelial mesenchymal transition through the MAPK pathway by inhibiting the expression of CCR7.Our results suggested that the therapeutic potential of let-7a as an antitumor and antimetastatic manager in prostate cancer and CCR7 may be regarded as a therapeutic target for the prostate cancer treatment.