Linc00657调控miR-30/Skp2促进宫颈癌恶性发展的机制研究

随着宫颈癌筛查的开展和宫颈癌疫苗的普及，宫颈癌的发病率和死亡率有所改善。但转移性的宫颈癌治疗效果差，需要寻求新的治疗靶点。Linc00657与多种肿瘤的发生发展有关，但在宫颈癌中的作用尚无人报道。前期研究，我们发现Linc00657过表达可以促进宫颈癌细胞的生长和迁移，而Linc00657的敲除抑制细胞的生长和迁移。本课题拟深入探讨Linc00657在宫颈癌发展中的分子机制。前期研究，我们发现Linc00657可以调控Skp2水平，而miR-30可以抑制宫颈癌细胞中Skp2的表达，因此我们推测：Linc00657可能是作为“分子海绵”吸附miR-30家族，抑制其对Skp2的降解，从而促进宫颈癌的进展。本项目拟从细胞水平，动物水平，临床标本展开研究，探讨Linc00657是否通过吸附miR-30家族促进Skp2的表达，从而加强宫颈癌的恶性进展，我们的研究可能为宫颈癌的治疗提供理论基础。

Screen detection and HPV vaccine for prevention have improved the prognosis of cervical cancer. However, the cervical cancer patients with metastasis have poor prognosis. Therefore, it is pivotal to develop the therapeutic treatment for better clinical management of cervical cancer. Linc00657 has been reported to be associated with various types of cancer development and progression. However, the function and role of Linc00657 in cervical cancer is unknown. Our preliminary data showed that Linc00657 overexpression promoted cell growth and motility, whereas Linc00657 downregulation inhibited cell growth and migration in cervical cancer. Therefore, we aim to explore the molecular mechanism of Linc00657-mediated tumor progression in cervical cancer. Our preliminary study showed that Linc00657 governed Skp2 expression, and miR-30 inhibited Skp2 level. Thus, we hypothesize that Linc00657 could sponge miR-30 to promote the growth and motility of cervical cancer cells through the upregulation of Skp2. In this proposal, we plan to define whether Linc00657 promotes tumor progression via sponging miR-30 and subsequent inhibition of Skp2 using cell culture, animal models and clinical samples. Our findings might shed insight onto new theoretical base and experimental evidence for discovery of novel therapeutic approaches of cervical cancer.