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微小 RNA-191-5p 通过靶向 EGR1 并激活 PI3K/AKT 信号通路促进骨肉瘤的发展。

MicroRNA-191-5p promotes the development of osteosarcoma via targeting EGR1 and activating the PI3K/AKT signaling pathway.

机构信息

Department of Orthopedics, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 May;23(9):3611-3620. doi: 10.26355/eurrev_201905_17783.

DOI:10.26355/eurrev_201905_17783
PMID:31114985
Abstract

OBJECTIVE

MicroRNA-191 (miR-191) has been reported to be abnormally expressed in human cancers and other diseases. The function of miR-191 was contradictory in different cancers. In the present study, we confirmed the specific function of miR-191-5p in osteosarcoma (OS).

PATIENTS AND METHODS

The effects of miR-191-5p on cellular behaviors of OS cells were investigated through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assay. The quantitative Real-time-polymerase chain reaction (qRT-PCR) was applied to examine the expressions of miR-191-5p and early growth response gene 1 (EGR1). Western blot and immunocytochemical assay were used to detect the protein expression of EGR1. The binding relationship between miR-191-5p and EGR1 was confirmed by Dual-Luciferase reporter gene assay. Xenograft tumor formation assay was conducted to examine the in vivo effect of miR-191-5p on tumor growth of OS.

RESULTS

MiR-191-5p was upregulated in OS tissues, which was related to poor prognosis of OS patients. Moreover, miR-191-5p promoted cell proliferation, migration and invasion by regulating EGR1 in OS. Furthermore, EGR1 was downregulated in OS tissues, which was associated with poor prognosis of OS patients. MiR-191-5p was found to promote epithelial-mesenchymal transition (EMT) and PI3K/AKT pathway, thus promoting the development of OS.

CONCLUSIONS

MiR-191-5p promoted the development of OS via targeting EGR1 and positively regulated the PI3K/AKT signaling pathway.

摘要

目的

已有研究报道,微小 RNA-191(miR-191)在人类癌症和其他疾病中异常表达。miR-191 在不同癌症中的功能具有差异性。本研究旨在证实 miR-191-5p 在骨肉瘤(OS)中的特定作用。

患者与方法

通过 MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)和 Transwell 实验研究 miR-191-5p 对 OS 细胞行为的影响。采用实时定量聚合酶链反应(qRT-PCR)检测 miR-191-5p 和早期生长反应基因 1(EGR1)的表达。采用 Western blot 和免疫细胞化学检测 EGR1 的蛋白表达。通过双荧光素酶报告基因实验证实 miR-191-5p 与 EGR1 之间的结合关系。通过异种移植肿瘤形成实验检测 miR-191-5p 对 OS 肿瘤生长的体内作用。

结果

miR-191-5p 在 OS 组织中上调,与 OS 患者的不良预后相关。此外,miR-191-5p 通过调节 EGR1 促进 OS 细胞的增殖、迁移和侵袭。此外,EGR1 在 OS 组织中下调,与 OS 患者的不良预后相关。研究发现 miR-191-5p 可促进上皮-间质转化(EMT)和 PI3K/AKT 通路,从而促进 OS 的发展。

结论

miR-191-5p 通过靶向 EGR1 促进 OS 的发展,并正向调节 PI3K/AKT 信号通路。

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