长链非编码RNAlnc-CC3作为细胞内β-catenin“调节器”增强宫颈癌侵袭转移的分子机制研究

宫颈癌的复发转移严重影响患者生存时间及质量。长链非编码RNA与肿瘤转移密切相关，是肿瘤分子机制研究的焦点领域。Lnc-CC3是申请者克隆的新lncRNA，最初发现其可提高Slug表达而增强宫颈癌的侵袭转移。后续研究显示lnc-CC3可与Slug的转录促进子β-catenin结合，并提高核内β-catenin的丰度，增强相关基因的表达。综合RNA pull down结果，推测lnc-CC3与β-catenin胞内定位及降解抑制的相关调控有关。因此本课题拟利用免疫共沉淀、免疫荧光、CRISPR-Cas9等技术揭示lnc-CC3导致细胞内β-catenin定位异常及降解抑制的原因，并通过体内外实验检测lnc-CC3相关蛋白结合序列缺失后宫颈癌侵袭转移能力的改变，阐明lnc-CC3作为β-catenin胞内“调节器”增强宫颈癌侵袭转移的分子机制，为肿瘤临床决策与基因治疗提供理论参考。

Patients with recurrent and metastasis cervical neoplasm always present poor quality of life and high death rate. Long noncoding RNA as a focus area in cancer research is closely related to tumor metastasis. We cloned a novel lncRNA, named lnc-CC3, can increase metastasis in cervical cancer by increasing Slug expression. Subsequent studies showed that lnc-CC3 can combine with β-catenin and enhance the abundance of β-catenin in nucleus, thus increasing the expression of tumor metastasis related genes like Slug. The analysis of RNA pull down assay suggested that lnc-CC3 may weaken the intercellular adhesion and β-catenin degradation by affecting the interaction of β-catenin with related proteins. Published reports showed that β-catenin is a promoter of Slug and play an important role in tumor metastasis. In this project, we will employ CO-IP, IF, CRISPR-Cas9 and other methods to reveal the cause of abnormal β-catenin localization and repressed degradation. And the metastasis ability change of lnc-CC3-mutant cervical cancer cell will be tested in vitro and vivo. The clarification of lnc-CC3 as an intracellular β-catenin modulator in increasing cervical cancer metastasis can provide new insights for tumor clinical decision-making and treatment.