通讯机构:
[Luo, Zhigang] U;Univ South China, Affiliated Hosp 2, Dept Urol, 35 Jiefang Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
Annexin A2;epithelial-mesenchymal transition;invasion;metastasis;microRNA;prostate cancer
摘要:
The present study investigated the molecular mechanism by which microRNA-206 (miR-206) targets Annexin A2 (ANXA2) expression and inhibits the invasion and metastasis of prostatic cancer cells through regulation of the epithelial-mesenchymal transition (EMT). Using bioinformatics analysis, miR-206 was identified as the most promising candidate miRNA that targeted ANXA2. Prostate tissue specimens from 60 patients with prostate cancer, 30 patients with metastatic prostate cancer and 20 patients with benign prostatic hyperplasia (BPH) were examined for ANXA2 protein expression by immunohistochemistry and western blotting and for miR-206 expression by reverse transcription-quantitative polymerase chain reaction. Additionally, human prostate cancer PC-3 cells were transfected with miR-206 mimics, miR-206 inhibitors or a negative control sequence, and expression of ANXA2, E-cadherin and N-cadherin was detected by western blotting. Transwell assays were performed to determine the effect of altered miR-206 expression on the invasive behavior of PC-3 cells. Bioinformatics analysis predicted complementary binding between miR-206 and ANXA2 mRNA. ANXA2 protein expression was detected in a significantly higher proportion of BPH tissues (95%, 19/20) when compared with prostate cancer tissues (51.7%, 31/60; P<0.05). Similarly, ANXA2 was expressed in a significantly higher proportion of metastatic prostate cancer samples than that of prostate cancer samples (P<0.05). Expression of miR-206 was higher than that of ANXA2 in prostate cancer samples, but lower in BPH samples. Inhibition of miR-206 expression in PC-3 cells upregulated ANXA2 and E-cadherin protein expression levels, downregulated N-cadherin and vimentin, and promoted cell invasion in vitro. These data suggested that binding between miRNA-206 and ANXA2 mRNA may regulate EMT signaling, thereby suppressing the invasion and metastasis of prostatic cancer cells.
作者机构:
[黄江波; 言彩红; 罗志刚; 刘利; 何群君; 龙向阳; 李建军] The Second Affiliated Hospital, University of South China, Hengyang, Hunan Province 421001, China;[Bao H.-Q.] Hunan Provincial Children’s Hospital, Dhangsha, Hunan Province 410007, China
通讯机构:
[Luo, Z.-G.] T;The Second Affiliated Hospital, University of South China, Hengyang, Hunan Province, China
作者机构:
[Luo, Zhigang; Song, Zhe; Li, Lian] Univ South China, Hosp 2, Dept Urol, Hengyang, Hunan, Peoples R China.;[Zheng, Liwen] Hengyang 1 Peoples Hosp, Dept Plast Surg, Hengyang, Hunan, Peoples R China.;[Chen, Tuo] Second Peoples Hosp Yueyang, Dept Urol, Yueyang, Hunan, Peoples R China.
通讯机构:
[Luo, Zhigang] U;Univ South China, Hosp 2, Dept Urol, Hengyang, Hunan, Peoples R China.
关键词:
*Dendritic cell;*Immunosuppression;*Regulatory T cell;*Renal transplantation;*Sinomenine
摘要:
OBJECTIVE: The immunosuppressive mechanism of sinomenine in organ allotransplantation was investigated, especially its effect of blocking dendritic cell (DC) maturation, which might influence the frequency of regulatory T cells (Tregs). METHODS: Bone marrow cells from male donor Wistar rats were induced to differentiate into DCs in vitro in the presence or absence of sinomenine, and characterized by flow cytometry. These two groups of DCs were respectively injected into male recipient Sprague-Dawley rats via the tail vein, at both high and low doses. Sprague-Dawley rats receiving saline injection were used as controls. Seven days later, renal transplantation was performed from donor Wistar rats to the recipient Sprague-Dawley rats. Seven days after transplantation, spleens were collected from the recipients. The proportions of Tregs and Foxp3(+) Tregs to CD4(+) T cells were determined using flow cytometry. RESULTS: With sinomenine treatment, the frequency of mature DCs was reduced, as indicated by lower expression of the surface markers CD80, CD86, and RT1B. In recipient Sprague-Dawley rats that received sinomenine-treated DCs before renal allotransplantation, the proportions of splenic Tregs and Foxp3(+) Tregs were significantly higher than in control recipients receiving saline or DCs without sinomenine treatment (all p<0.05). A high dose of sinomenine-treated DCs (10(6) cells) had a more obvious effect in increasing Tregs than the low dose (10(5) cells) (p<0.05). CONCLUSION: Pre-transplant infusion of donor-derived sinomenine-induced maturation arrested DCs could result in the increase of Foxp3(+) Tregs in the spleens of recipients after renal allotransplantation.
作者机构:
[陈仙; 刘俊; 阳宁] Department of Urology, Second Affiliated Hospital, University of South China, Hengyang 421001, China;[王玲] Hunan University of Environment and Biology, Hengyang 421001, China;[罗志刚] Department of Urology, Second Affiliated Hospital, University of South China, Hengyang 421001, China. *Corresponding author, E-mail: luo6398@sina.com