膀胱癌相关环状RNA-3(BCRC-3)调控miRNA-182-5p/p27通路在膀胱癌中的作用及机制研究

Circular RNA(circRNA)is stably expressed in various species with a tissue/cell specific manner. Recent studies have revealed that circRNA can exert crucial regulatory function as efficient miRNA sponge. Our previous study has first successfully identified bladder cancer related circRNA-3(BCRC-3) which relatively low expressed in human bladder cancer tissues through circRNA deep-sequencing. Preliminary studies show that BCRC-3 is predominately localized in the cytoplasm. Over-expression of BCRC-3 effectively inhibits proliferation of bladder cancer cells in vitro. BCRC-3 contains three predicted binding sites of miR-182-5p, and further confirm the direct combination of BCRC-3 and miR-182-5p through RNA pull-down assay. miR-182-5p can enhance the proliferative ability of bladder cancer cell through inhibiting the expression of p27. In the project, we will further reveal the function of BCRC-3 and underlying mechanism of BCRC-3/miR-182-5p interaction in regulation of p27 expression, as well as provide a novel strategy and target for the treatment of bladder cancer.

环状RNA（circRNA）是一类结构稳定、表达丰富且具有组织及细胞相关性的环形RNA分子。近来研究揭示了circRNA可作为高效的"microRNA分子海绵"来发挥重要的调控作用。申请人前期通过对人膀胱癌和配对正常膀胱组织进行环状RNA高通量测序，成功鉴定出膀胱癌中相对低表达的膀胱癌相关环状RNA-3（BCRC-3），发现其在细胞浆内富集。初步研究显示：过表达BCRC-3可在体外抑制膀胱癌细胞增殖。通过生物信息学分析发现BCRC-3含有3个miRNA-182-5p结合位点，并进一步通过RNA pull-down实验证实二者可直接结合，而miR-182-5p可通过抑制p27蛋白的表达来发挥潜在的生物学功能。本课题拟在前期研究的基础上，深入研究膀胱癌中BCRC-3的生物学功能，以及其与miR-182-5p相互调控、影响下游基因p27表达的机制，以期为膀胱癌的靶向治疗提供新策略和靶点。