非编码RNA circ-Ccnb1调控Cdc25A/CyclinD1/Bclaf1信号通路在乳腺癌中的作用及分子机制研究

circRNA是非编码RNA领域的研究热点和前沿。近期申请人在Nature子刊Cell Death Differ（IF 8.339）中的2项成果，其一入选Molecular Biology & Genetics高被引论文，及Cancer Lett（IF 6.508）中的1项成果，表明circRNA在mRNA及基因表达调控中发挥着重要作用。近期基因芯片结果显示circ-Ccnb1在乳腺癌组织中表达特异性显著下调；其过表达能够抑制Cdc25A；并可以被Cyclin D1抗体RIP沉淀；质谱结果也表明其探针能够沉淀Bclaf1。基于此课题将深入研究circ-Ccnb1调控Cdc25A/Cyclin D1/Bclaf1信号通路在三阴乳腺癌中的作用及分子机制；利用其阻断寡核苷酸进行确证实验；进而找到抑制肿瘤细胞周期及增殖的新开关，为肿瘤的发生机制提供新的理论依据；为肿瘤诊断和靶向治疗提供策略及途径。

Nowadays, circRNA is research frontier and focus in the field of noncoding RNA. Recently, the applicant published two research achievements in Cell Death and Differentiation (IF 8.339), one of which was selected into the Highly Cited Paper of Molecular Biology & Genetics, and one achievement in Cancer Letters (IF 6.508), indicating that circRNA plays an important role in regulation of mRNA and gene expression network. .Lately, microarray results showed that circ-Ccnb1 was down-regulated in breast cancer tissue; over expression of circ-Ccnb1 could reduce the expression of Cdc25A; circ-Ccnb1 could be precipitated by Cyclin D1 antibody in RIP, and mass spectrometry results showed that circ-Ccnb1 probe could precipitate Bclaf1. Based on these results, we will further study the regulation of circ-Ccnb1 on triple negative breast cancer, and use blocking-oligo of circ-Ccnb1 binding site to confirm its functions. And study the interaction mechanism between circ-Ccnb1 and Cdc25A / Cyclin D1/ Bclaf1. Finally, we hope to find a new switch to inhibit tumor cell cycle and proliferation, expand a new theoretical basis for tumor pathogenesis, and provide a new strategy and approach for tumor diagnosis and molecular target therapy.