文献类型：会议

作　　者：Bian-Li Dang,Wen Ding,Ye Zhang,Jin-Zhou Huang,Qing-Yu He, Guang-RongYan

作者单位：暨南大学生命科学技术学院生命与健康工程研究院

会议文献：中国病理生理学会第十三届肿瘤、第十四届免疫专业委员会学术会议论文集

会议名称：中国病理生理学会第十三届肿瘤、第十四届免疫专业委员会学术会议

会议日期：20120614

会议地点：中国河南郑州

主办单位：中国病理生理学会肿瘤专业委员会;中国病理生理学会免疫专业委员会

出版日期：20120614

语　　种：中文

摘　　要：Although miRNAs have been found to play an important role in the carcinogenesis,their molecular mechanism remains largely unknown because of our limited understanding of miRNA target genes.We demonstrated that miR-373 expression level was enhanced in metastasic breast cancer cells MDA-MB-435 and MDA-MB-23 1,metastasic lymph tissues of breast cancer,compared to the nonmetastasic cells MCF-7,breast carcinoma in situ.MiR-373 overexpression could induce migration and invasion of breast cancer cells MCF-7,whereas the inhibition of miR-373 level supressed the migration and invasion of breast cancer cells MDA-MB- 435 and MDA-MB-23 1.We used SILAC quantitative proteomics to fully identify miR-373-regulated proteins and globally found its target genes.Totally 3666 proteins were identified,and 335 proteins were found to be regulated by miR-373.Among the 192 miR-373-down-regulated proteins,27 were predicted to have at least one potential match site at their 3' UTR for miR-373 seed sequence by TargetScan and miRanda programm.However,miR-373 did not affect the mRNA level of the five selected candidate targets,TXNIP,TRPS1,RABEP1,GRHL2 and HIP1,suggesting that the protein expressions were regulated by miR-373 via translational inhibition instead of mRNA degradation.Luciferase and mutation assays validated that TXNIP and ITGA2,which have been previously reported to be invovled in cancer invasion and metastasis,were novel miR-373 target genes.The protein level of TXNIP and ITGA2 were inversely correlated with the level of miR-373 and the ability of migration and invasion of breast cancer.Silencing of TXNIP could inhibit migration and invasion of breast cancer,and Silencing of ITGA2 could inhibit migration of breast cancer instead of invasion,consistent with the effect of miR-373 overexpression.TXNIP or ITGA2 overexpression could block the inhibtion effect of miR-373 on invasion and metastasis,while the TXNIP or ITGA2 expressing plasmids containing 3'-UTR did not affect the miR-373 inhibition,suggesting that the downregulation of

关 键 词：miR-373  PROTEOMICS Target gene  Breast Cancer  METASTASIS

分 类 号：R737.9]