摘要目的 探讨miR-23a( Homo sapiens miR-23a)与转移抑制因子1(metastasis suppressor 1,MTSS1)在结肠癌中的表达情况及其临床意义.方法 运用荧光素报告载体系统检测miR-23a直接调控的靶基因并采用Transwell侵袭实验检测miR-23a对人结肠癌SW620细胞的侵袭能力.收集结肠癌患者手术标本92例,癌旁组织作为正常对照,分别运用原位杂交、免疫组织化学EliVision法检测结肠癌组织及癌旁组织中miR-23a、MTSS1的表达水平,并对二者进行相关性分析.结果 MTSS1是miR-23a直接调控的靶基因,miR-23a下调MTSS1蛋白的表达,增强结肠癌细胞侵袭能力.在92例结肠癌组织中miR-23a阳性表达率为87.0％( 80/92),MTSS1蛋白阳性表达率为17.4％(16/92),分别与癌旁对照组比,差异有统计学意义(P ＜0.01)；miR-23a的表达随着结肠癌临床分期演进(P =0.029)和浸润深度增加而增加(P=0.000),且有淋巴结转移的miR-23a的表达显著高于无淋巴结转移组(P=0.041)；MTSS1的表达随着结肠癌临床分期演进(P=0.027)和浸润深度增加而下调(P=0.017),且有淋巴结转移的MTSS1的表达显著低于无淋巴结转移组(P=0.009)；相关性分析表明,miR-23a表达与MTSS1的表达呈显著负相关(r=-0.594,P=0.013).结论 miR-23a通过靶向抑制MTSS1促进结肠癌SW620细胞生长、侵袭转移；miR-23a的高表达和MTSS1蛋白低表达可能是肠黏膜恶性转变以及结肠癌发生浸润转移的重要生物学标志,检测二者对预测结肠癌浸润转移有重要意义.

abstractsObjective To investigate the expression of miR-23a and metastasis suppressor 1 (MTSS1) and their clinical significance in colon carcinoma.Methods A total of 92 cases of colon carcinomas were collected with both the tumor and paired normal tissue samples for the study.The miR-23a targeting MTSS1 was evaluated by luciferase reporter vector.Cell invasion potential was evaluated by transwell invasion assay.In-situ hybridization and immunohistochemistry were used to detect miR-23a and MTSS1 expression.Results MiR-23a downregulated the expression of MTSS protein and enhanced the invasiveness of colon carcinoma.The expression rates of miR-23a and MTSS1 were 87.0％ (80/92) and 17.4％ (16/92) in colon carcinoma cases,respectively ( P ＜ 0.01 ).The up-regulation of miR-23a expression was associated with an advanced clinical stage ( P =0.029) and depth of invasion ( P =0.000).The expression of miR-23a was higher in the tumors with lymph node metastasis than those without (P =0.041 ).Down-regulation of MTSS1 expression was associated with an advanced clinical stage (P=0.027) and depth of invasion (P =0.017).The expression of MTSS1 was lower in the tumors with lymph node metastasis than those without (P =0.009).The expression of miR-23a had significantly negative correlation with that of MTSS1 ( r =- 0.594,P =0.013 ).Conclusions MiR-23a expression promotes colon carcinoma cell growth,invasion and metastasis through inhibition of MTSS gene.Both the low expression of MTSS1 and high expression of miR-23a may serve as important biological markers for the malignant phenotypes of colon cancer,such as invasion and metastasis.