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微小RNA-762通过靶向LZTS1调控参与胃癌发生发展的PI3K/AKT和Hippo信号通路的激活。

MiR-762 regulates the activation of PI3K/AKT and Hippo pathways involved in the development of gastric cancer by targeting LZTS1.

作者信息

Yu Kuaiyun, Zhu Heng

机构信息

Department of General Surgery, Yantaishan Hospital Yantai 264001, Shandong, China.

Department of Digestive, The Fourth People's Hospital of Ji'nan Ji'nan 250031, Shandong, China.

出版信息

Am J Transl Res. 2022 Jul 15;14(7):5050-5058. eCollection 2022.

Abstract

OBJECTIVE

MiR-762 has been confirmed as a tumor promoter in multiple tumors, while few reports illustrate its role in gastric cancer (GC). Thus, this research aimed to investigate whether miR-762 is involved in GC development.

METHODS

MiR-762 expression in the tumor tissues from GC patients and GC cell lines was analyzed by qRT-PCR. The assays including CCK-8, transwell, and flow cytometry were performed to reveal the functions of miR-762 in GC. The target genes of miR-762 were searched by online databases, and then were verified by dual-luciferase reporter assay. Western blot was performed to investigate the activation of PI3K/AKT and Hippo pathways in GC.

RESULTS

MiR-762 was aberrantly upregulated in the tumor tissues and cell lines, and miR-762 silencing could effectively reduce the viability and promote apoptosis of GC cell lines. The study identified LZTS1 as a target gene of miR-762. It was also found that the effects of miR-762 on GC cells could be reversed by LZTS1, and miR-762 could upregulate the activation of the PI3K/AKT pathway but inhibit the Hippo pathway by targeting LZTS1.

CONCLUSION

MiR-762 activates PI3K/AKT and suppresses Hippo pathways to boost GC proliferation and invasion by targeting LZTS1.

摘要

目的

MiR - 762已被证实为多种肿瘤中的肿瘤促进因子,而关于其在胃癌(GC)中作用的报道较少。因此,本研究旨在探讨MiR - 762是否参与GC的发生发展。

方法

采用qRT - PCR分析GC患者肿瘤组织和GC细胞系中MiR - 762的表达。进行CCK - 8、transwell和流式细胞术等实验,以揭示MiR - 762在GC中的功能。通过在线数据库搜索MiR - 762的靶基因,然后用双荧光素酶报告基因检测进行验证。采用蛋白质免疫印迹法研究GC中PI3K/AKT和Hippo信号通路的激活情况。

结果

MiR - 762在肿瘤组织和细胞系中异常上调,沉默MiR - 762可有效降低GC细胞系的活力并促进其凋亡。该研究确定LZTS1为MiR - 762的靶基因。还发现LZTS1可逆转MiR - 762对GC细胞的影响,且MiR - 762可通过靶向LZTS1上调PI3K/AKT信号通路的激活,但抑制Hippo信号通路。

结论

MiR - 762通过靶向LZTS1激活PI3K/AKT信号通路并抑制Hippo信号通路,从而促进GC的增殖和侵袭。

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