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miR-200b-3p 通过靶向 ABCA1 在肺腺癌中发挥癌基因作用。

MiR-200b-3p Functions as an Oncogene by Targeting ABCA1 in Lung Adenocarcinoma.

机构信息

Department of thoracic surgery, 7th Medical Center of Peoples Liberation Army General Hospital, Beijing, China.

出版信息

Technol Cancer Res Treat. 2019 Jan-Dec;18:1533033819892590. doi: 10.1177/1533033819892590.

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

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。

方法

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

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。

结论

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。

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