机构地区:[1]山西医科大学基础医学院,太原030001 [2]解放军总医院第八医学中心呼吸学部研究所,北京100091 [3]浙江大学医学院附属第二医院泌尿外科,杭州310009 [4]解放军总医院第三医学中心泌尿外科学部,北京100143
出 处:《解放军医学杂志》2022年第1期26-32,共7页Medical Journal of Chinese People's Liberation Army
基 金:国家自然科学基金青年科学基金(81802804);军队医学科技青年培育计划孵化项目(19QNP060);解放军总医院“优青”培育专项(2020-YQPY-006)。
摘 要:目的探讨CYFIP2基因在肾透明细胞癌(KIRC)增殖及迁移中的作用。方法利用TCGA数据库分析CYFIP2基因在KIRC中的表达及与临床病理因素的相关性。将KIRC细胞系786-O转染siRNA-CYFIP2对CYFIP2基因进行敲低,并利用携带有CYFIP2基因的病毒颗粒感染786-O细胞构建CYFIP2基因稳定过表达体系。将CYFIP2基因敲低后的786-O细胞作为敲低组(siRNA-CYFIP2,si-CYFIP2),并设置相应的对照组siNC;CYFIP2基因过表达后的786-O细胞作为过表达组(over expressionCYFIP2,OE-CYFIP2),并设置相应的对照组OE-NC。采用细胞增殖实验及Transwell实验分析敲低或过表达CYFIP2基因后786-O细胞增殖活性及迁移能力的差异。结果 TCGA数据库中CYFIP2在KIRC中的表达明显降低(P<0.0001),且随肿瘤分期分级进展而降低(P<0.05);发生淋巴结转移和远处转移后,CYFIP2基因亦呈低水平表达(PN<0.05,PM<0.01);CYFIP2高表达组患者5年生存率较低表达组明显升高(P<0.05)。细胞增殖活性实验及Transwell实验结果显示,与si-NC组比较,si-CYFIP2组增殖活性明显增强(P<0.0001),细胞迁移数目明显增多(P<0.0001),而OE-CYFIP2组的增殖活性及迁移能力与OE-NC组比较均明显降低(P<0.001)。结论 CYFIP2基因对KIRC细胞的增殖及迁移能力具有明显的抑制作用,可能具有潜在的抑癌作用,可作为后续KIRC临床诊疗的候选基因之一。Objective To investigate the role of CYFIP2 gene in proliferation and migration of renal clear cell carcinoma(KIRC). Methods The TCGA database was used to analyze the expression of CYFIP2 gene in KIRC and the correlation between the expression and clinicopathological factors. The KIRC cell line 786-O was transfected with siRNA-CYFIP2 to knockdown the CYFIP2 gene, and the CYFIP2 gene stable overexpression system was constructed by infecting 786-O cells with viral particles carrying the CYFIP2 gene. The 786-O cells were used as the knockdown group(siRNA-CYFIP2, si-CYFIP2) after the CYFIP2 gene was knockdown, and set the corresponding control group si-NC;the 786-O cells were used as the overexpression group(Over Expression-CYFIP2, OE-CYFIP2) after performing CYFIP2 gene overexpression, and set the corresponding control group OE-NC.Subsequently, cell proliferation assays and Transwell assays were performed to analyze the differences in proliferative activity and migration ability of 786-O cells after knockdown or overexpression of CYFIP2 gene. Results The expression of CYFIP2 in KIRC was significantly lower(P<0.0001) in the TCGA database and decreased with the progression of tumor staging(P<0.05);CYFIP2 gene was also expressed at a low level after the occurrence of lymph node metastasis and distal metastasis(PN<0.05, PM<0.01);the5-year survival rate of patients was significantly higher in the group with high CYFIP2 expression than that in the group with low expression(P<0.05). The cell proliferation activity assay showed that the proliferation activity was significantly enhanced in siCYFIP2 group than that in si-NC group(P<0.0001) and the number of cell migration was significantly increased(P<0.0001), while the proliferation activity and migration ability of OE-CYFIP2 group were significantly inhibited(P<0.001) compared with that of OE-NC group. Conclusion The CYFIP2 gene had a significant inhibitory effect on the proliferation and migratory ability of KIRC cells and may have a potential antitumor effect, which can b
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