miR-877-3p在前列腺癌细胞中调节雄激素受体AR3的表达及其功能研究

AR3,a major AR splice variant,is newly cloned and idenified in human prostate tissues which plays a key role in maintaining androgen-independent growth of prostate cancer cells.Recently, it has been demonstrated that microRNAs are involved in human tumorigenesis through regulating genes related to cell proliferation, differentiation or apoptosis, thus revealing a new layer in the molecular architecture of human cancer. Unfortunately, by now there is no report on which microRNAs are involved in the regulation of AR3 in prostate cancer cells. Based on the inverse correlation between the expression of miR-877-3p and AR in human prostate tissues and the characteristics of miR-877-3p binding to human AR3 3'-UTR, bioinformatics method is used to predict the potential miRNAs involved in the regulation of AR3 in prostate cancer cells.After the primary screening, we identified miR-877-3p is involved in the regulation of human AR3 and found the effects of miR-877-3p on proliferation,migration and invation in prostate cancer cells. Cancer related 10-pathway reporter assay kits were used to study the function of miR-877-3p in the progression of prostate cancer cells and possible melecular mechanisms. Successful completion of the proposed research will enable us to gain new insights into the role of miR-877-3p involved in the regulation of AR3 in prostate cancer biology. This study may lay foundation or provide very important information for development of new therapeutic agents based on microRNAs for prostate cancer.

AR3是新近克隆和鉴定的主要雄激素受体剪接变体，它在维持前列腺癌雄激素非依赖生长时起着重要作用。而作为调控基因表达的miRNA被越来越多的研究证明其可通过调节参与细胞周期、增殖和凋亡等相关基因的表达参与肿瘤发生。目前国内外对能调控AR3表达的miRNA的研究还未见报道。本研究根据miR-877-3p与AR3在前列腺癌细胞中的表达呈负相关及其与AR3 3'-UTR结合的特点，借助生物信息学方法对能调控AR3表达的miRNA进行预测和实验鉴定。结果显示miR-877-3p参与了AR3的表达调控，且其对前列腺癌细胞的增殖、迁移和侵润等方面存在影响。并用肿瘤相关的10个信号通路荧光素酶报告基因系统鉴定miR-877-3p的功能及其在前列腺癌发病时可能的作用机制。从而揭示前列腺癌中能调控AR3的miR-877-3p的新视野，并可能为开发基于miRNA的新型前列腺癌治疗药物提供重要参考资料。

AR3是新近克隆和鉴定的主要雄激素受体剪接变体，它在维持前列腺癌雄激素非依赖生长时起着重要作用。而作为调控基因表达的miRNA被越来越多的研究证明其可通过调节参与细胞周期、增殖和凋亡等相关基因的表达参与肿瘤发生。目前国内外对能调控AR3表达的miRNA的研究还未见报道。本研究根据miR-877-3p与AR3在前列腺癌细胞中的表达呈负相关及其与AR3 3'-UTR结合的特点，借助生物信息学方法对能调控AR3表达的miRNA进行预测和实验鉴定。结果显示miR-877-3p参与了AR3的表达调控，且其对前列腺癌细胞的增殖、迁移和侵润等方面存在影响。并用肿瘤相关的10个信号通路荧光素酶报告基因系统鉴定miR-877-3p的功能及其在前列腺癌发病时可能的作用机制。从而揭示前列腺癌中能调控AR3的miR-877-3p的新视野，并可能为开发基于miRNA的新型前列腺癌治疗药物提供重要参考资料。