环状RNAcirc_001506靶向miR-200c调控EGFR信号通路在中耳胆脂瘤角质形成细胞过度增殖中的机制研究

中耳胆脂瘤是以角质形成细胞过度增殖为特征的疾病，其增殖的内在分子机制不明。环状RNA可通过竞争性结合miRNA进而调控靶基因表达。前期研究发现环状RNAcirc_001506在中耳胆脂瘤中表达上调，在胆脂瘤角质形成细胞过度增殖中起重要作用，但具体作用机制尚未明确。生物信息学分析发现circ_001506和EGFR序列中均存在miR-200c的结合位点，前期实验发现miR-200c在中耳胆脂瘤中表达下调，而EGFR表达上调。据此我们首次提出假说：circ_001506在中耳胆脂瘤中表达上调，并通过靶向下调miR-200c活性进而激活EGFR信号通路，导致胆脂瘤角质形成细胞过度增殖。本课题将通过体内、外实验揭示circ_001506靶向miR-200c调控EGFR信号通路在中耳胆脂瘤角质形成细胞过度增殖中的作用，为明确胆脂瘤上皮过度增殖的分子机制提供实验依据，并为防治其过度增殖开辟新思路。

Middle ear cholesteatoma is a disease characterized by excessive proliferation of keratinocytes, and the underlying molecular biological mechanism of its proliferation is unknown. Circular RNA (circRNA) can bind miRNA competitively to regulate target gene expression. Our previous research found that circRNA circ_001506 was significantly up-regulated in middle ear cholesteatoma and played an important role in the keratinocyte hyper-proliferation. Nevertheless, the concrete mechanism of activation remains unclear. Bioinformatics analysis found that miR-200c binding site exists both in circ_001506 and EGFR sequence. Furthermore, we discovered that miR-200c expression was down-regulated and EGFR was up-regulated significantly in middle ear cholesteatoma. Accordingly, we hypothesize that circ_001506 is up-regulated in the middle ear cholesteatoma, and by targeting down-regulation of miR-200c activity to activate the EGFR signaling pathway, it eventually leads to excessive proliferation of middle ear cholesteatoma keratinocytes. In this study, we will investigate the mechanism of circ_001506 targeting miR-200c to regulate the EGFR signaling pathway in the hyperproliferation of keratinocytes of middle ear cholesteatoma through in vivo and in vitro experiments. So that it could clarify the molecular mechanism of keratinocyte hyper-proliferation and explore a novel target for the prevention and treatment of keratinocyte hyper-proliferation of middle ear cholesteatoma.