CNN2通过上皮-间质转化促进结直肠癌细胞的侵袭与迁移  

CNN2 promotes invasion and migration of colorectal cancer cells through epithelial-mesenchymal transformation

作　　者：郭静宇 王祎丽 千新来[1] 朱会芳 GUO Jing-yu;WANG Yi-li;QIAN Xin-lai;ZHU Hui-fang(Department of Pathology,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,China)

机构地区：[1]新乡医学院第三附属医院病理科,新乡453003

出　　处：《临床与实验病理学杂志》2022年第8期909-914,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：河南省科技攻关项目(212102310621)。

摘　　要：目的 探讨结直肠癌(colorectal cancer,CRC)中CNN2的表达及其对细胞的侵袭和迁移的作用。方法 采用qRT-PCR法检测CNN2基因在CRC不同细胞系中的表达,应用免疫组化法检测CNN2蛋白在CRC及对应癌旁正常组织中的表达,并分析其与CRC临床病理特征的关系。应用siRNA技术干扰CRC细胞中CNN2的表达,采用Transwell侵袭实验和划痕愈合实验检测CRC细胞的侵袭和迁移能力;利用Western blot法和免疫组化法检测EMT在CNN2促进CRC细胞株中的作用。结果 30例CRC中CNN2高表达23例,低表达7例。CNN2的表达与患者性别、年龄和分化程度无关(P>0.05),而与肿瘤淋巴结转移及TNM分期有关(P<0.05)。在CRC细胞株HCT116和HCT-8中干扰CNN2后,CRC细胞的侵袭(侵袭率分别为:si-NC组vs si-CNN2组:137.67±5.25 vs 51±5.35、178.33±12.28 vs 89±3.27)和迁移能力(迁移率分别为:si-NC组vs si-CNN2组:55.4%±0.9%vs 24.2%±4.3%、57.3%±1.6%vs 24.05%±2.65%)均明显下降(P<0.05)。Western blot结果显示,干扰CNN2后,CRC细胞株HCT116和HCT-8中的上皮标志物E-cadherin的表达水平显著增强(分别为:1.615±0.047、1.229±0.073),而间质标志物N-cadherin及vimentin的表达(N-cadherin分别为:0.597±0.181 5、0.451±0.003 5;vimentin分别为:0.723±0.047 5、0.676±0.134)明显下降(P<0.05);且在CRC组织中CNN2与E-cadherin的表达呈负相关(r=-0.866,P<0.01)。结论 CNN2在CRC中高表达,并通过EMT促进CRC细胞的侵袭和迁移。Purpose To investigate the effect of CNN2 on invasion and migration of colorectal cancer cells(CRC) and its mechanism.Methods qRT-PCR was used to detect the expression of CNN2 gene in different CRC cell lines,and immunohistochemistry was used to detect the expression of CNN2 protein in CRC and corresponding adjacent normal tissues.Transwell invasion assay and scratch healing assay were used to analyze the invasion and migration ability after CRC cells were transfected with si-CNN2 and its negative control.Western blot and immunohistochemistry were used to analyze the mechanism of EMT in promoting invasion and migration on CRC cells by CNN2.Results Of the 30 CRC patients,23 had high CNN2 expression and 7 had low expression.CNN2 expression was correlated with lymph node metastasis and TNM stage(P<0.05).However,CNN2 expression was not associated with sex,age and differentiation(P>0.05).Transwell invasion assay and scratch healing assay showed that knockdown CNN2 inhibited the invasion and migration ability of HCT116 and HCT-8 cells(invasion cells of si-NC vs si-CNN2 group:137.67±5.25 vs 51±5.35,178.33±12.28 vs 89±3.27,respectively in HCT116 or HCT-8 cells,migration rate:si-NC vs si-CNN2 group:55.4%±0.9% vs 24.2%±4.3%,57.3%±1.6% vs 24.05%±2.65%,respectively in HCT116 or HCT-8 cells).Western blot results showed that the expression of epithelial marker E-cadherin was significantly increased after CNN2 interference in HCT116 and HCT-8 cells(1.615±0.047,1.229±0.073,respectively in HCT116 or HCT-8 cells),and the expression of interstitial markers N-cadherin and vimentin decreased significantly(N-cadherin:0.597±0.181 5,0.451±0.003 5,vimentin:0.723±0.047 5,0.676±0.134,respectively in HCT116 or HCT-8 cells)(P<0.05).Meanwhile,CNN2 was negatively correlated with E-cadherin in CRC tissues(r=-0.866,P<0.01).Conclusion CNN2 is overexpressed in CRC,and it promotes the invasion and migration of CRC cells by EMT.

关 键 词：结直肠肿瘤 CNN2 侵袭 迁移 EMT 

分 类 号：R735.3[医药卫生—肿瘤]