关键词: 乳腺癌, 反式激活反应RNA结合蛋白2, A激酶锚定蛋白12, 肿瘤转移

Abstract: Objective To study the role and mechanism of trans-activation response RNA-binding protein 2 (TARBP2) in post-transcriptional regulation of the expression of AKAP12, a metastasis suppressor gene, in breast cancer cells. Methods The expression of TARBP2 in breast tumor tissues and potential relationship between TARBP2 expression and tumor metastasis were analyzed by bioinformatics methods. Bioinformatics methods were used to analyze the correlation between TARBP2 and AKAP12 expression in different breast cancer datasets. MDA-MB-231 cells were transfected with GFP-tagged TARBP2 plasmids by Lipofectamine 2000 and screening with G418. Lung metastasis in tumor-bearing nude mice was detected by HE staining. RT-qPCR was used to test the expression of AKAP12 and its half-life. Luciferase assay was carried out to determine whether the transcript decay was mediated through targeting the 3′UTR. EMSA assay was performed to detect the physically binding of TARBP2 with stem-loop structure of AKAP12. Results The high expression of TARBP2 in human breast tumor tissue was closely related to lymph node metastasis. TARBP2 over-expression in MDA-MB-231 cells significantly promoted tumor metastasis in vitro(P＜0.05). TARBP2 inhibited the expression of AKAP12(P＜0.01) and reduced its mRNA half-life(P＜0.05). TARBP2 significantly suppressed luciferase activity of AKAP12 3′UTR reporter(P＜0.05) and bound to the stem-loop structure. There was a significant negative correlation between TARBP2 and AKAP12 expression in human breast cancer samples(P＜0.001). Conclusions TARBP2-mediated inhibition of AKAP12 gene expression might be one of the mechanisms of TARBP2 promoting breast cancer metastasis.

Key words: breast cancer, TARBP2, AKAP12, tumor metastasis