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microRNA-152 通过靶向 E2F 转录因子 3 抑制人骨肉瘤细胞的增殖和侵袭。

MicroRNA-152 Suppresses Human Osteosarcoma Cell Proliferation and Invasion by Targeting E2F Transcription Factor 3.

机构信息

The First Hospital of Jilin University, Changchun, P.R. China.

出版信息

Oncol Res. 2018 Jun 11;26(5):765-773. doi: 10.3727/096504017X15021536183535. Epub 2017 Aug 15.

Abstract

MicroRNA-152 (miR-152) expression has been reported to be downregulated in osteosarcoma (OS). However, the role of miR-152 in OS is not well documented. In the present study, we aimed to explore the function and underlying mechanism of miR-152 in OS. We found that miR-152 was underexpressed in OS tissues and cell lines. Decreased miR-152 was inversely correlated with lymph node metastasis and advanced clinical stage. Overexpression of miR-152 significantly inhibited cell proliferation, colony formation, migration, and invasion of OS cells. Bioinformatics analyses showed that miR-152 directly targeted E2F transcription factor 3 (E2F3), as further confirmed by a dual-luciferase reporter assay. E2F3 expression was upregulated and inversely correlated with miR-152 expression level in human OS tissues. Moreover, the inhibitory effects of miR-152 on OS growth and invasion were attenuated by E2F3 overexpression. Taken together, our findings indicated that miR-152 reduced OS growth and invasion by targeting E2F3 and provided new evidence of miR-152 as a potential therapeutic target for OS.

摘要

miR-152(miR-152)的表达在骨肉瘤(OS)中被报道下调。然而,miR-152 在 OS 中的作用尚未得到充分证实。在本研究中,我们旨在探讨 miR-152 在 OS 中的功能和潜在机制。我们发现 miR-152 在 OS 组织和细胞系中表达下调。miR-152 的减少与淋巴结转移和晚期临床分期呈负相关。miR-152 的过表达显著抑制了 OS 细胞的增殖、集落形成、迁移和侵袭。生物信息学分析表明,miR-152 可直接靶向 E2F 转录因子 3(E2F3),进一步通过双荧光素酶报告基因实验得到证实。E2F3 在人 OS 组织中的表达上调,与 miR-152 的表达水平呈负相关。此外,E2F3 的过表达减弱了 miR-152 对 OS 生长和侵袭的抑制作用。总之,我们的研究结果表明,miR-152 通过靶向 E2F3 减少 OS 的生长和侵袭,为 miR-152 作为 OS 潜在治疗靶点提供了新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4dc/7844728/61fc0ef67a70/OR-26-765-g001.jpg

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