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微小 RNA-370 通过直接靶向 PAQR4 抑制胃癌细胞的增殖、侵袭和 EMT。

MicroRNA-370 inhibits the proliferation, invasion and EMT of gastric cancer cells by directly targeting PAQR4.

机构信息

Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Jilin, 130033, China.

Department of Nephrology, First Hospital of Jilin University, Jilin, 130021, China.

出版信息

J Pharmacol Sci. 2018 Oct;138(2):96-106. doi: 10.1016/j.jphs.2018.08.004. Epub 2018 Aug 25.

Abstract

It has been reported that PAQR4 (Progestin and AdipoQ Receptor 4) expression is closely associated with progression of many cancers and microRNA (miRNA) processing. However, the effects and its precise mechanisms of PAQR4 in gastric cancer (GC) have not been well clarified. Our study aimed to explore the interaction between PAQR4 and miR-370 in GC. In our study, we found that the miR-370 level was significantly down-regulated in GC tissues and cell lines, and the expression of PAQR4 was dramatically increased. Interestingly, the low miR-370 level was closely associated with up-regulated PAQR4 expression in GC tissues. Moreover, introduction of miR-370 dramatically suppressed proliferation, invasion and EMT of GC cells. Whereas, miR-370 knockdown increased the proliferation, invasion and EMT in GC cells. We demonstrated that miR-370 could directly target PAQR4 by using both bioinformatics analysis and luciferase reporter assay. In addition, PAQR4 silencing had the similar effects with miR-370 overexpression on GC cells. Overexpression of PAQR4 in GC cells partially reversed the inhibitory effects of miR-370 mimic. miR-370 inhibited cell proliferation, invasion and EMT of GC cells by directly down-regulating PAQR4 expression, and miR-370 targeting PAQR4 was responsible for inhibition of the proliferation, invasion and EMT of GC cells.

摘要

据报道,PAQR4(孕激素和脂联素 Q 受体 4)的表达与许多癌症的进展密切相关,并且参与 miRNA(微小 RNA)加工。然而,PAQR4 在胃癌(GC)中的作用及其确切机制尚未阐明。本研究旨在探讨 GC 中 PAQR4 与 miR-370 之间的相互作用。在本研究中,我们发现 miR-370 在 GC 组织和细胞系中的水平显著下调,而 PAQR4 的表达显著增加。有趣的是,GC 组织中 miR-370 水平低与 PAQR4 表达上调密切相关。此外,miR-370 的引入可显著抑制 GC 细胞的增殖、侵袭和 EMT。然而,miR-370 敲低可增加 GC 细胞的增殖、侵袭和 EMT。我们通过生物信息学分析和荧光素酶报告基因检测证实 miR-370 可直接靶向 PAQR4。此外,PAQR4 沉默与 miR-370 过表达对 GC 细胞具有相似的作用。GC 细胞中 PAQR4 的过表达部分逆转了 miR-370 模拟物的抑制作用。miR-370 通过直接下调 PAQR4 表达抑制 GC 细胞的增殖、侵袭和 EMT,miR-370 靶向 PAQR4 负责抑制 GC 细胞的增殖、侵袭和 EMT。

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