eIF3C基因调控Ephrin信号通路在卵巢癌增殖转移中的作用及机制研究

High Invasion and metastasis are the important factors of poor clinical treatment and high mortality in patients with ovarian cancer, the molecular mechanism is still unclear. In recent years, it has been found that eIF3C, a member of Eukaryotic initiation factors (eIF3) subfamily, is highly expressed in tumor and is closely related to tumor occurrence and development. The current research shows that Ephrin signaling pathway plays an important role in regulating the proliferation and metastasis of tumor cells . Applicant's preliminary study found that: eIF3C were highly expressed in epithelial ovarian cancer and ovarian cancer cell lines, and is closely related to cell proliferation and metastasis. Bioinformatics analysis suggested that the Ephrin signaling pathway could be significantly inhibited ，and the proliferation ability of ovarian cancer cells was also significantly decreased when the eIF3C gene was knocked down. Therefore, the research hypothesis is proposed: eIF3C may promote the proliferation and metastasis of ovarian cancer cells by regulating the Ephrin signaling pathway. In the present study, We deeply explore the role and mechanism of eIF3C/ Ephrin signaling pathway in the proliferation and metastasis of ovarian cancer cells through cell experiments, combination of animal models and clinical data，to provide new ideas and scientific basis for finding molecular targets for monitoring and evaluating the curative effect of ovarian cancer.

卵巢癌的高侵袭转移特性是临床治疗效果差、死亡率高的重要原因，其分子机制至今仍然不清。近年来研究发现真核翻译起始因子3（eIF3）亚家族成员 eIF3C 在肿瘤细胞中高表达并和肿瘤的发生、发展密切相关；Ephrin信号通路在参与调控肿瘤细胞增殖、转移的过程中扮演重要角色。申请人前期研究发现：eIF3C在上皮性卵巢癌组织及卵巢癌细胞系中呈高表达；沉默卵巢癌细胞中eIF3C基因表达后，生物信息学分析提示Ephrin信号通路被显著抑制，卵巢癌细胞增殖能力也明显减弱。据此提出研究假设：eIF3C可能通过调控Ephrin信号通路来影响卵巢癌细胞的增殖及转移能力。本项目拟从细胞和动物水平结合卵巢癌临床病例研究深化揭示eIF3C/Ephrin通路在卵巢癌细胞增殖和转移中的作用机制，为寻找卵巢癌病情监控和疗效评价的分子靶点提供新的思路与科学依据。

卵巢癌的高侵袭转移特性是临床治疗效果差、死亡率高的重要原因，其分子机制至今仍然不清。近年来研究发现真核翻译起始因子3（eIF3）亚家族成员 eIF3C 在肿瘤细胞中高表达并和肿瘤的发生、发展密切相关，但其在卵巢癌中的作用机制尚不明确。课题组用80例卵巢癌组织进行免疫组化分析后发现eIF3c的过表达与患者的不良预后相关。eIF3c敲低后可显著抑制卵巢癌细胞SKOV3、HO-8910的增殖和侵袭能力，促进细胞的凋亡。基因芯片分析发现在卵巢癌中eIF3c沉默显著上调了217个基因，下调了340个基因。在对差异基因进行KEGG、GSEA富集分析后发现p53信号通路与eIF3c有关，并证实eIF3C基因敲低上调了P53信号通路，抑制细胞的侵袭和增殖，促进细胞的凋亡。这些结果表明，eIF3c通过异常调节翻译起始，在人卵巢癌细胞的增殖和生存中发挥重要作用，其机制可能是通过调节p53信号通路来调节卵巢癌细胞的增殖和迁移。这些结果为进一步深入研究人卵巢癌发生发展的信号通路提供了实验方向，为寻找卵巢癌病情监控和疗效评价的分子靶点提供新的思路与科学依据。