神经源性外泌体通过miR-155-5p/SOX1/Wnt/β-catenin轴调控宫颈癌嗜神经侵袭的作用机制研究

宫颈癌嗜神经侵袭可能给保留盆腔自主神经的广泛性子宫切除术带来盆底或盆腔复发的风险，因此厘清宫颈癌嗜神经侵袭的分子机制是目前宫颈癌个体化手术治疗所急需解决的问题。申请人前期研究发现，外周神经胶质细胞雪旺细胞来源的CCL2促进宫颈癌细胞增殖、迁移、侵袭和上皮间质转化，同时肿瘤细胞上调雪旺细胞基质金属蛋白酶表达促进基质溶解，雪旺细胞与宫颈癌细胞交互作用形成肿瘤神经微环境促进嗜神经侵袭（Front Oncol. 2020）。进一步研究发现，背跟神经节细胞培养上清促进宫颈癌细胞侵袭，背跟神经节细胞源性外泌体通过miR-155-5p/SOX1轴激活Wnt/β-catenin信号通路。本项目拟在前期研究基础上，阐述神经源性外泌体通过miR-155-5p/SOX1/Wnt/β-catenin轴调控宫颈癌细胞嗜神经侵袭分子机制，指导保留盆腔自主神经的广泛性子宫切除术患者筛查方案的建立奠定理伦基础。

Tumor perineural invasion (PNI) may bring high risk of pelvic floor or pelvic recurrence to the individualized extensive nerve sparing radical hysterectomy (NSRH). Therefore, it is crucial to clarify the molecular mechanism of PNI in the individualized surgery of cervical cancer. In our previous study, we found that CCL2 derived from peripheral Schwann cells promote the proliferation, migration, invasion and epithelial-mesenehymal transition of cervical cancer cells, while cancer cells could up-regulate the expression of Schwann cell matrix metalloproteinase to promote matrix dissolution, and Schwann cells interact with cervical cancer cells to form a tumor microenvironment to promote PNI (Front.Oncol. 2020). Further study showed that the supernatant of dorsal root ganglion (DRG) cells promoted the invasion of cervical cancer cells, and the exosomes of DRG cells activated Wnt/β-catenin signaling pathway through miR-155-5p/SOX1 axis. On the basis of our previous studies, this project intends to elaborate the molecular mechanism of neurogenic exosomes modulating the PNI of cervical cancer cells through miR-155-5p/SOX1/Wnt/β-catenin axis, thus providing experimental evidence for the establishment of clinical screening program for patients with extensive nerve sparing radical hysterectomy (NSRH) .