目的：探究lnc RNA MIR17HG在宫颈癌组织和细胞中的表达水平与临床意义，分析其对宫颈癌HeLa细胞恶性生物学行为和裸鼠移植瘤生长的影响及其可能的作用机制。方法：采用TCGA数据库分析MIR17HG和TRIM25在宫颈癌中的表达水平，并分析MIR17HG和TRIM25表达水平与患者的临床病理特征的相关性。收集2019年8月至2020年12月山东大学齐鲁医院收治的30例宫颈癌患者的肿瘤组织和癌旁组织，体外培养人正常宫颈上皮End1/E6E7细胞、人乳腺癌细胞HeLa、C33A、CasKi和SiHa，采用qPCR技术检测宫颈癌组织和细胞中的MIR17HG表达水平。采用脂质体将MIR17HG过表达质粒或敲降质粒分别转染宫颈癌HeLa细胞，CCK-8法、克隆形成实验和Transwell实验分别检测MIR17HG对HeLa细胞的增殖、集落形成、迁移和侵袭能力的影响。采用ENCORI预测并用qPCR和WB法验证MIR17HG对TRIM25的靶向调控作用。采用Targetscan和荧光报告系统验证miR-377与TRIM25之间的靶向关系。采用WB法检测MIR17HG对HeLa细胞中AKT信号通路相关蛋白表达的影响。构建MIR17HG过表达HeLa细胞裸鼠移植瘤模型，观察移植的瘤生长。结果：宫颈癌组织中MIR17HG和TRIM25 mRNA均呈高表达（均P<0.05），宫颈癌细胞中MIR17HG表达水平高于人正常宫颈上皮细胞（P<0.01或P<0.001）。MIR17HG和TRIM25的高表达与宫颈癌的恶性程度有关（P<0.05）。与对照组相比，MIR17HG过表达组HeLa细胞的增殖、克隆形成、迁移和侵袭能力均显著升高，而MIR17HG敲降组则相反（P<0.05或P<0.01）。MIR17HG可能通过抑制miR-377来上调TRIM25的表达。MIR17HG过表达组HeLa细胞中AKT信号通路相关蛋白表达水平升高。MIR17HG过表达组裸鼠移植瘤的生长水平高于对照组（P<0.01）。结论：MIR17HG在宫颈癌组织和细胞中呈高表达，过表达MIR17HG能够促进HeLa细胞的恶性生物学行为、加速裸鼠移植瘤的生长，其可能是通过抑制miR-377上调TRIM25激活AKT通路来发挥其促癌的作用。

Objective: To investigate the expression level and clinical significance of lncRNA MIR17HG in cervical cancer tissues and cells, and to analyze its effect on the malignant biological behaviors of cervical cancer HeLa cells and the growth of transplanted tumors in nude mice and its possible mechanism. Methods: The TCGA database was used to analyze the expression levels of MIR17HG and TRIM25 in cervical cancer tissues, and to analyze the correlation between their expression levels and the clinicopathological characteristics of patients. The tumor tissues and paracancerous tissues of 30 cervical cancer patients admitted to Qilu Hospital of Shandong University from August 2019 to December 2020 were collected. Human normal cervical epithelial End1/E6E7 cells and human breast cancer cells HeLa, C33A, CasKi and SiHa were cultured in vitro. qPCR was used to detect the expression level of MIR17HG in cervical cancer tissues and cells. The MIR17HG overexpression plasmid or knockdown plasmid was transfected into cervical cancer HeLa cells by liposomes respectively, and then the impact of MIR17HG on the proliferation, colony formation,migration, and invasion abilities on HeLa cells were detected by CCK-8 assay, colony formation assay and Transwell assay,respectively. The targeted regulation of MIR17HG on TRIM25 was predicted by ENCORI and verified by qPCR and WB methods.Targetscan and fluorescent reporter systems were used to verify the targeting relationship between miR-377 and TRIM25. WB method was used to detect the effect of MIR17HG on the expression of AKT signaling pathway-related proteins in HeLa cells. A nude mouse xenograft model of MIR17HG overexpressing HeLa cells was constructed, and the growth of the transplanted tumor was observed.Results: Both MIR17HG and TRIM25 mRNA were highly expressed in cervical cancer tissues (both P<0.05), and the expression level of MIR17HG in cervical cancer cells was higher than that in human normal cervical epithelial cells (P<0.01 or P<0.001). The high expression of MIR17HG and TRIM25 was associated with the malignancy of cervical cancer (P<0.05). Compared with the control group, the proliferation, colony formation, migration, and invasion abilities of HeLa cells in the MIR17HG overexpression group were significantly increased, while the opposite was true in the MIR17HG knockdown group (P<0.05 or P<0.01). MIR17HG may upregulate the expression of TRIM25 by inhibiting miR-377. The expression levels of AKT signaling pathway-related proteins in HeLa cells in the MIR17HG overexpression group were increased. The growth level of xenograft tumors in the MIR17HG overexpression group was higher than that in the control group (P<0.01). Conclusion: MIR17HG is highly expressed in cervical cancer tissues and cells. Overexpression of MIR17HG can promote the malignant biological behaviors of HeLa cells and accelerate the growth of transplanted tumors in nude mice. MIR17HG may exert its cancer-promoting effect by inhibiting miR-377 and upregulating TRIM25 to activate the AKT pathway.

山东省重点研发计划资助项目（No. 2019GSF108121）