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

Downregulated miR-144-3p contributes to progression of lung adenocarcinoma through elevating the expression of EZH2.
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DOI:
10.1002/cam4.1714
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发表时间:
2018-11
期刊:
影响因子:
4
通讯作者:
Chen T
Chen T
中科院分区:
医学3区
文献类型:
--
作者:
Liu C;Yang Z;Deng Z;Zhou Y;Gong Q;Zhao R;Chen T

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本研究的目的是探讨miR-144 - 3 p和EZH 2之间的关系,以及它们之间的相互作用对肺腺癌(LUAD)细胞增殖和侵袭力的影响。采用qRT-PCR方法检测LUAD组织和正常组织中miR-144 - 3 p和EZH 2的表达水平。利用双荧光素酶报告基因测定来验证miR-144 - 3 p和EZH 2之间的靶向关系。MTT法和集落形成实验检测LUAD细胞的存活率和增殖能力,transwell实验检测miR-144 - 3 p和EZH 2对LUAD细胞侵袭力的影响。通过Western blot测定VEGFA、MMP 2和MMP 9的蛋白表达水平。此外,建立异种移植肿瘤模型以验证miR-144 - 3 p对体内肿瘤形成和EZH 2、VEGFA、MMP 2和MMP 9表达的影响。miR-144 - 3 p在LUAD组织中下调,miR-144 - 3 p过表达抑制LUAD细胞的增殖和侵袭力。EZH 2是miR-144 - 3 p的靶点,在LUAD细胞中高度表达。敲低EZH 2基因可抑制LUAD细胞的增殖和侵袭。miR-144 - 3 p表达增加对体内LUAD肿瘤形成具有抑制作用。miR-144 - 3 p的过表达通过靶向EZH 2阻碍LUAD细胞的增殖和侵袭。
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). 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. 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. Overexpression of miR‐144‐3p impeded the propagation and invasiveness of LUAD cells by targeting EZH2.
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