m6A修饰的LINC01411通过CD47介导的肿瘤免疫逃逸促进宫颈癌淋巴结转移

淋巴结转移是宫颈癌转移的主要方式，但发生机制尚未完全阐明。研究发现，肿瘤细胞发生上皮间质转化（EMT）后会激活CD47信号逃避巨噬细胞吞噬，促进转移发生。我们前期分析宫颈癌细胞EMT前后的RNA和MeRIP测序数据，发现m6A修饰的lncRNA-LINC01411可促进宫颈癌细胞CD47蛋白N端焦谷氨酸形成，抑制巨噬细胞吞噬作用，促使EMT后的宫颈癌细胞发生免疫逃逸。由此我们推断：m6A修饰的LINC01411可通过CD47介导的肿瘤细胞免疫逃逸促进宫颈癌淋巴结转移。因此本项目拟进一步明确m6A修饰的LINC01411介导肿瘤细胞免疫逃逸在宫颈癌淋巴结转移中的作用；阐明m6A修饰的LINC01411激活CD47信号、促进肿瘤细胞免疫逃逸的具体分子机制。本研究将从m6A修饰的lncRNA调控肿瘤细胞免疫逃逸的角度，揭示宫颈癌淋巴结转移的新机制，为宫颈癌患者的精准治疗提供新的潜在靶点。

Lymph nodes are the most common sites for cervical cancer to metastasize, but the underlying molecular mechanism has not been fully clarified. Studies have found that cancer cells undergoing epithelial-mesenchymal transition (EMT) activate CD47 signal to escape from macrophage phagocytosis, thus promoting cancer metastasis. We analyzed RNA and MeRIP sequencing data of cervical cancer cells undergoing EMT and identified a key lncRNA, LINC01411, with aberrant m6A modification. Our preliminary research showed that LINC01411 with m6A modification promoted pyroglutamate formation in the N-terminus of CD47 and inhibited macrophage phagocytosis, leading to immune escape of cervical cancer cells. Thus, we speculate that LINC01411 with m6A modification promotes lymph node metastasis of cervical cancer through CD47 mediated immune escape. Therefore, this project intends to further verify the role of LINC01411-mediated immune escape in lymph node metastasis; and to elucidate the molecular mechanism by which LINC01411 with m6A modification activates CD47 signal and promotes immune escape. From the perspective of immune escape mediated by a lncRNA, this project might reveal new mechanisms of lymph node metastasis and provide a potential target for precision treatment of cervical cancer.