MicroRNA-149对肺鳞状细胞癌转移能力的影响及分子机制研究

Effect of miR-149 on metastasis of lung squamous cell carcinoma and its molecular mechanism

目的研究microRNA-149(miR-149)在肺鳞状细胞癌(LSCC)的临床意义及其对细胞迁移和侵袭的作用。方法选取2010年1月-2015年12月西南医科大学附属医院收治的60例LSCC患者的癌灶及癌旁组织。采用实时荧光定量聚合酶链反应(qRT-PCR)检测miR-149在LSCC及癌旁组织中的表达。通过转染miR-149模拟物升高LSCC细胞系NCI-H226中miR-149的表达,划痕愈合试验检测过表达miR-149对NCI-H226细胞迁移的影响,Transwell小室探究miR-149对NCI-H226侵袭的影响。qRT-PCR及Western Blot检测miR-149过表达对NCI-H226细胞中叉头盒蛋白M1(FOXM1)及其靶基因基质金属蛋白酶2(MMP-2)表达的影响。结果 miR-149在LSCC中表达水平低于癌旁组织(P<0.05);过表达miR-149能够降低NCI-H226细胞的迁移及侵袭能力(P<0.05)。过表达miR-149能够下调其下游靶点FOXM1 mRNA和蛋白表达水平,抑制FOXM1靶基因MMP-2的表达(P<0.05)。结论 miR-149在LSCC中呈低表达,miR-149通过抑制FOXM1/MMP-2信号通路来抑制LSCC的细胞转移能力。

Objective To investigate the expression of miR-149 in lung squamous cell carcinoma(LSCC)and its role in tumor migration and invasion.Methods Sixty cases of LSCC and matched tumor adjacent tissues were collected in the Affiliated Hospital of Southwest Medical University between January 2010 and December 2015.The expression levels of miR-149 were detected by qRT-PCR.miR-149 mimics were transfected into NCI-H226 cells.Migration and invasion were determined by wound-healing assay and Transwell assay,respectively.The expressions of FOXM1 and MMP-2 were detected by real-time PCR and Western blot.Results The expression of miR-149 was down-regulated in the LSCC tissues(P<0.05).Over-expression of miR-149 inhibited migration and invasion of NCI-H226 cells(P<0.05).Moreover,the expressions of FOXM1 and MMP-2 were decreased after miR-149 overexpression(P<0.05).Conclusions miR-149 is down-regulated in LSCC.miR-149 inhibits metastasis of LSCC by inhibiting FOXM1/MMP-2 signaling pathway.