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

摘要:

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。

Abstract:

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.