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巨噬细胞移动抑制因子靶向 miR-451 对结肠癌肿瘤抑制作用和肿瘤干细胞调控的研究。

The tumour suppressor effects and regulation of cancer stem cells by macrophage migration inhibitory factor targeted miR-451 in colon cancer.

机构信息

Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, Australia; Department of Pathology and Forensic Medicine, College of Medicine, University of Babylon, Iraq.

Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, Australia.

出版信息

Gene. 2019 May 20;697:165-174. doi: 10.1016/j.gene.2019.02.046. Epub 2019 Feb 22.

DOI:10.1016/j.gene.2019.02.046
PMID:30802541
Abstract

BACKGROUND

This study aimed to investigate the impact of miR-451 on the biological behaviours of colon cancer cells along with its targets interactions.

METHOD

The levels of miR-451 were tested in colon cancer cell lines (SW480 and SW48). Multiple functional and immunological assays were performed to analyse miR-451 induced growth changes in-vitro and downstream effects on target proteins.

RESULTS

Overexpression of miR-451 in colon cancer cells led to reduced cell proliferation, increased apoptosis and decrease accumulation of the cells at the G0/G1 phase of the cell cycle. In addition, a significant increase in the number of the cells was noted in the G2-M phase of cell cycle. Moreover, miR-451 reduced the expression of Oct-4, Sox-2 and Snail indicating its role in stem cell and epithelial-mesenchymal transition (EMT) regulation. An inverse correlation between miR-451 and macrophage migration inhibitory protein (MIF) protein expression occurred in colon cancer cells. Furthermore, restoration the level of miR-451 in colon cancer cells inhibits tumour spheres formation.

CONCLUSION

miR-451 has tumour suppressor effects in vitro, which can inhibit the cancer-related signalling pathways in colon cancer.

摘要

背景

本研究旨在探讨 miR-451 对结肠癌细胞生物学行为的影响及其靶基因相互作用。

方法

检测结肠癌细胞系(SW480 和 SW48)中 miR-451 的水平。进行多种功能和免疫测定,以分析 miR-451 在体外诱导的生长变化及其对靶蛋白的下游影响。

结果

结肠癌细胞中 miR-451 的过表达导致细胞增殖减少、凋亡增加以及细胞周期 G0/G1 期的细胞积累减少。此外,细胞周期的 G2-M 期的细胞数量显著增加。此外,miR-451 降低了 Oct-4、Sox-2 和 Snail 的表达,表明其在干细胞和上皮-间充质转化(EMT)调控中的作用。在结肠癌细胞中,miR-451 与巨噬细胞移动抑制因子(MIF)蛋白表达呈负相关。此外,恢复结肠癌细胞中 miR-451 的水平可抑制肿瘤球体形成。

结论

miR-451 在体外具有肿瘤抑制作用,可抑制结肠癌细胞中的癌症相关信号通路。

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