miR-320在结直肠癌中的表达及意义  

Dysregulation of microRNA-320 expression in colorectal cancer

作　　者：张丹华[1] 董明[1] 周建平[1] 

机构地区：[1]中国医科大学附属第一医院普通外科教研室胃肠外科,辽宁省沈阳市110001

出　　处：《世界华人消化杂志》2013年第32期3592-3597,共6页World Chinese Journal of Digestology

基　　金：辽宁省教育厅科技基金资助项目;No.2008809~~

摘　　要：目的:探讨miR-320与结直肠癌临床病理因素间的关系,寻找其下游调控蛋白,及对结直肠癌细胞化疗敏感性的影响.方法:采用RT-PCR检测83例结直肠癌组织及癌旁组织中miR-320的表达,结合结直肠癌临床病理指标分析其相关性,用miR-320病毒转染HCT-116及ClonA1两株结直肠癌细胞系,Western blot检测其调控蛋白C-Jun氨基端激酶(c-Jun N-terminal kinase,JNK)的表达,采用四甲基偶氮唑蓝显色法(methyl thiazolyl tetrazolium,MTT)检测LV-miR-320细胞株与阴性对照组间对5-氟尿嘧啶(5-fluorouracil,5-Fu)化疗的敏感性.结果:83例结直肠癌标本中miR-320的表达明显低于癌旁组织表达(P=0.012).miR-320表达与肿瘤分化程度相关,高分化组织中表达较中低分化组织高,与局部浸润深度及TNM分期相关(P=0.012,P=0.004),但不受患者性别、年龄、肿瘤的大小及位置的影响;获得LV-miR-320稳定转染细胞株及阴性对照株(negative control,NC),Western blot结果显示LV-miR-320组JNK表达明显降低;LV-miR-320组HCT-116及ClonA1半数抑制浓度(IC50值)分别为11.34 g/mL和12.56 g/mL,NC组IC50值分别为24.73 g/mL和25.34 g/mL(P=0.023,P=0.018).结论:miR-320在结直肠癌组织中呈低表达,其在结直肠癌细胞中过表达后,可明显抑制JNK蛋白翻译,而显著增加细胞对5-Fu化疗的敏感性.提示miR-320在结直肠癌的发生发展及治疗中起重要作用.AIM： To detect the expression of miR-320 in colorectal cancer to reveal its relationship with clinical and pathological characteristics of colorectal cancer, and to investigate the effect of miR-320 overexpression on chemosensitivity of colorectal cancer cell lines. METHODS： The expression of miR-34a was detected by real-time PCR in CRC tissues and tumor-adjacent non-tumorous tissues. HCT-116 and ClonA1 cell lines were transfected with ei- ther a LV-miR-320 or a negative control （NC）. C-Jun N-terminal kinase （JNK） expression was measured by Western blot after up-regulation of miR-320. The chemosensitivity of cell lines was tested by MTT assay.RESULTS： MiR-320 expression was significantly down-regulated in CRC cancer tissues compared with tumor-adjacent tissues （P = 0.012）. The expression of miR-320 was correlated with de- gree of differentiation, local invasion and TNM stage （P = 0.045, 0.012, 0.04）. Overexpression of miR-320 significantly suppressed the expression of JNK, and the ICs0 values for the LV-miR-320 group were significantly lower than those for the negative control group （11.34 vs 24.73, 12.56 vs 25.34, P = 0.023, 0.018）. CONCLUSION： MiR-320 is frequently down- regulated in CRC, which can repress the expres- sion of JNK and modulate chemosensitivity of colorectal cancer cell lines. MiR-320 may play an important role in carcinogenesis and therapy of colorectal cancer.

关 键 词：miR-320 C—Jun氨基端激酶 结直肠癌 化疗敏感性 

分 类 号：R735.3[医药卫生—肿瘤]