下调的 miR-144-3p 通过上调 EZH2 的表达促进肺腺癌的进展。

Downregulated miR-144-3p contributes to progression of lung adenocarcinoma through elevating the expression of EZH2.

机构信息

Department of Nuclear Medicine, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, China.

Departments of Orthopaedics, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, China.

出版信息

Cancer Med. 2018 Nov;7(11):5554-5566. doi: 10.1002/cam4.1714. Epub 2018 Oct 2.

OBJECTIVES

The intention of our study was to investigate the relationship between miR-144-3p and EZH2 as well as the effects of their interaction on cell propagation and invasiveness in lung adenocarcinoma (LUAD).

METHODS

The expression levels of miR-144-3p and EZH2 in LUAD tissues and normal tissues were determined by qRT-PCR. The dual-luciferase reporter assay was utilized to validate the targeting relationship between miR-144-3p and EZH2. MTT assay and colony formation assay were performed to evaluate the viability and propagation of LUAD cells, while the effects of miR-144-3p and EZH2 on LUAD cell invasiveness were confirmed by transwell assay. Protein expression levels of VEGFA, MMP2, and MMP9 were measured by Western blot. Furthermore, xenograft tumor models were established to verify the effects of miR-144-3p on tumor formation and EZH2, VEGFA, MMP2 and MMP9 expressions in vivo.

RESULTS

miR-144-3P was downregulated in LUAD tissues, and overexpression of miR-144-3p inhibited propagation and invasiveness of LUAD cells. EZH2 was a target of miR-144-3p and was highly expressed in LUAD cells. Knockdown of EZH2 could suppress the propagation and invasion of LUAD cells. Increased miR-144-3p expression exerted an inhibitory effect on LUAD tumor formation in vivo.

CONCLUSION

Overexpression of miR-144-3p impeded the propagation and invasiveness of LUAD cells by targeting EZH2.

目的

本研究旨在探讨 miR-144-3p 与 EZH2 之间的关系及其相互作用对肺腺癌（LUAD）细胞增殖和侵袭的影响。

方法

采用 qRT-PCR 检测 LUAD 组织和正常组织中 miR-144-3p 和 EZH2 的表达水平。利用双荧光素酶报告基因实验验证 miR-144-3p 与 EZH2 之间的靶向关系。MTT 法和集落形成实验评估 LUAD 细胞的活力和增殖能力，Transwell 实验验证 miR-144-3p 和 EZH2 对 LUAD 细胞侵袭能力的影响。Western blot 法检测 VEGFA、MMP2 和 MMP9 蛋白表达水平。此外，建立异种移植瘤模型验证 miR-144-3p 对体内肿瘤形成以及 EZH2、VEGFA、MMP2 和 MMP9 表达的影响。

结果

miR-144-3p 在 LUAD 组织中表达下调，过表达 miR-144-3p 抑制 LUAD 细胞的增殖和侵袭能力。EZH2 是 miR-144-3p 的靶基因，在 LUAD 细胞中高表达。敲低 EZH2 可抑制 LUAD 细胞的增殖和侵袭能力。增加 miR-144-3p 的表达对体内 LUAD 肿瘤形成具有抑制作用。