SNHG17通过与转录因子E2F1结合激活CENPE促进肾透明细胞癌细胞增殖、迁移和侵袭

SNHG17 activates CENPE by binding to transcription factor E2F1 to promote the proliferation,migration and invasion of clear cell renal cell carcinoma cells

目的:探讨SNHG17通过与转录因子E2F1结合激活CENPE对肾透明细胞癌细胞增殖、迁移和侵袭的影响。方法:生信分析SNHG17、E2F1和CENPE在肾透明细胞癌肿瘤组织中的表达,生信分析三者的调控关系。qRT-PCR检测SNHG17、E2F1和CENPE的mRNA水平。Western blot检测E2F1和CENPE的蛋白表达。CCK-8、Transwell实验分别检测细胞增殖、迁移和侵袭情况。RIP实验验证SNHG17与E2F1的结合关系;ChIP实验检测E2F1与CENPE的结合关系。构建异种瘤模型验证SNHG17对肾透明细胞癌生长的影响。结果:SNHG17和CENPE在肾透明细胞癌组织和细胞系中的表达水平均显著上调。沉默SNHG17转染肾透明细胞后,癌细胞的增殖、迁移和侵袭受到明显抑制。体内实验也验证了沉默SNHG17抑制肾透明细胞癌的生长。此外,RIP实验显示SNHG17能够与转录因子E2F1结合。ChIP实验检测转录因子E2F1与CENPE启动子区的结合,结果表明E2F1能够显著富集在CENPE的启动子区。体外功能实验表明SNHG17通过招募E2F1激活CENPE表达从而促进肾透明细胞癌细胞的增殖和转移。结论:SNHG17招募E2F1上调CENPE,促进肾透明细胞癌细胞的致瘤性。

Objective:To investigate the effect of SNHG17 on the proliferation,migration and invasion of clear cell renal cell carcinoma cells by activating CENPE in combination with transcription factor E2F1.Methods:The expression of SNHG17,E2F1 and CENPE in clear cell renal cell carcinoma tissue was analyzed,and their regulatory relationship was analyzed by bioinformatics.The mRNA levels of SNHG17,E2F1 and CENPE were detected by qRT-PCR.The protein expression of E2F1 and CENPE was detected by Western blot.CCK-8 and Transwell assay were used to detect cell proliferation,migration and invasion.RIP experiment verified the binding relationship between SNHG17 and E2F1.The binding relationship between E2F1 and CENPE was detected by ChIP experiment.The effect of SNHG17 on the growth of clear cell renal cell carcinoma was investigated by establishing a xenograft tumor model.Results:The expression levels of SNHG17 and CENPE were significantly up-regulated in clear cell renal cell carcinoma tissues and cell lines.After silencing SNHG17 was transfected into renal clear cells,the proliferation,migration and invasion of cancer cells were significantly inhibited.In vivo experiments also confirmed that silencing SNHG17 inhibited the growth of clear cell renal cell carcinoma.In addition,RIP experiments showed that SNHG17 can bind to the transcription factor E2F1.The binding of transcription factor E2F1 to the CENPE promoter region was detected by ChIP assay.The results showed that E2F1 could be significantly enriched in the CENPE promoter region.In vitro functional experiments showed that SNHG17 promoted the proliferation and metastasis of clear cell renal cell carcinoma cells by activating CENPE expression through recruiting E2F1.Conclusion:SNHG17 recruits E2F1 to up-regulate CENPE and promote tumogenicity of clear cell renal cell carcinoma cells.