Department of thoracic surgery, 7th Medical Center of Peoples Liberation Army General Hospital, Beijing, China.
Technol Cancer Res Treat. 2019 Jan-Dec;18:1533033819892590. doi: 10.1177/1533033819892590.
The aim of this study was to investigate the microRNA-200b-3p expression in lung adenocarcinoma and the possible functional associations of microRNA-200b-3p with cell proliferation, migration, and invasion.
Quantitative real-time polymerase chain reaction was used to detect the expression of microRNA-200b-3p in lung adenocarcinoma samples and in the human lung adenocarcinoma cell lines A549 and H1299. A549 and H1299 cells were transfected with either a microRNA-200b-3p mimic or a negative control microRNA or either an empty vector or an adenosine triphosphate-binding cassette transporter A-1 overexpression vector. A Cell Counting Kit-8 assay was employed to assess the ability of cell proliferation. Transwell assays and transwell-Matrigel invasion assay were, respectively, utilized to assess the capacity of migration and invasion in A549 and H1299 cells.
The results showed that microRNA-200b-3p expression was significantly upregulated in tumor tissues compared with that in adjacent normal tissues. Overexpression of microRNA-200b-3p promoted lung adenocarcinoma cell proliferation and metastasis. Furthermore, adenosine triphosphate-binding cassette transporter A-1 was a direct target of microRNA-200b-3p, and this binding was verified by luciferase reporter analysis. Overexpression of adenosine triphosphate-binding cassette transporter A-1 obviously suppressed lung adenocarcinoma cell proliferation, migration, and invasion. Lung adenocarcinoma cell phenotypes induced by microRNA-200b-3p overexpression could be partially remitted by the co-overexpression of microRNA-200b-3p and adenosine triphosphate-binding cassette transporter A-1.
This study first identified that microRNA-200b-3p is upregulated in lung adenocarcinoma cells and associated with cell proliferation and metastasis. MicroRNA-200b-3p promoted lung adenocarcinoma cell proliferation and metastasis by suppressing adenosine triphosphate-binding cassette transporter A-1. MicroRNA-200b-3p may function as a novel molecular marker and therapeutic target for lung adenocarcinoma treatment.
本研究旨在探讨 microRNA-200b-3p 在肺腺癌中的表达及其与细胞增殖、迁移和侵袭的可能功能关联。
采用实时定量聚合酶链反应检测肺腺癌组织及人肺腺癌细胞系 A549 和 H1299 中 microRNA-200b-3p 的表达。用 microRNA-200b-3p 模拟物或阴性对照 microRNA 转染 A549 和 H1299 细胞,或用空载体或三磷酸腺苷结合盒转运蛋白 A1 过表达载体转染。采用细胞计数试剂盒-8 法评估细胞增殖能力。分别采用 Transwell 法和 Transwell-Matrigel 侵袭实验评估 A549 和 H1299 细胞的迁移和侵袭能力。
结果显示,与邻近正常组织相比,肿瘤组织中 microRNA-200b-3p 的表达显著上调。microRNA-200b-3p 的过表达促进肺腺癌细胞增殖和转移。此外,三磷酸腺苷结合盒转运蛋白 A1 是 microRNA-200b-3p 的直接靶标,这一结合通过荧光素酶报告分析得到了验证。三磷酸腺苷结合盒转运蛋白 A1 的过表达明显抑制肺腺癌细胞的增殖、迁移和侵袭。microRNA-200b-3p 过表达诱导的肺腺癌细胞表型可通过 microRNA-200b-3p 和三磷酸腺苷结合盒转运蛋白 A1 的共过表达部分逆转。
本研究首次发现,microRNA-200b-3p 在肺腺癌细胞中上调,并与细胞增殖和转移相关。microRNA-200b-3p 通过抑制三磷酸腺苷结合盒转运蛋白 A1 促进肺腺癌细胞增殖和转移。microRNA-200b-3p 可能作为肺腺癌治疗的新的分子标志物和治疗靶点。