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长链非编码RNA MEG3通过miR-141-3p/RBMS3轴调控乳腺癌的增殖和凋亡。

LncRNA MEG3 regulates breast cancer proliferation and apoptosis through miR-141-3p/RBMS3 axis.

作者信息

Dong Shiliang, Ma Minrui, Li Ming, Guo Yuexin, Zuo Xiaoxiao, Gu Xiaobin, Zhang Mingzhi, Shi Yonggang

机构信息

Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

出版信息

Genomics. 2021 Jul;113(4):1689-1704. doi: 10.1016/j.ygeno.2021.04.015. Epub 2021 Apr 9.

Abstract

Maternally expressed 3 (MEG3) and RNA binding motif single stranded interacting protein 3 (RBMS3) are abnormally expressed in breast cancer susceptibility genes (BRCA), but the mechanism of the two in breast cancer (BC) is unclear. By performing in vivo and in vitro experiments, we found that MEG3 and RBMS3 were low-expressed, negatively correlated with high-expressed miR-141-3p, were positively correlated with each other in BC. MEG3 targeted miR-141-3p, and miR-141-3p targeted RBMS3. MEG3, which was mainly distributed in BC cytoplasm, could down-regulate miR-141-3p and up-regulate RBMS3, and reverse effect of miR-141-3p on related gene expressions and on promoting cancer development. Overexpressed MEG3 inhibited growth of xenografts, promoted cell apoptosis via regulating apoptosis related factors, and up-regulated RBMS3 expression but down-regulated miR-141-3p. The findings of this study showed that MEG3 inhibited proliferation and promoted apoptosis of BC cells through the miR-141-3p/RBMS3 axis, and MEG3 inhibited growth of xenografts through miR-141-3p.

摘要

母源表达基因3(MEG3)和RNA结合基序单链相互作用蛋白3(RBMS3)在乳腺癌易感基因(BRCA)中异常表达,但二者在乳腺癌(BC)中的作用机制尚不清楚。通过体内和体外实验,我们发现MEG3和RBMS3在BC中低表达,与高表达的miR-141-3p呈负相关,二者之间呈正相关。MEG3靶向miR-141-3p,而miR-141-3p靶向RBMS3。主要分布于BC细胞质中的MEG3可下调miR-141-3p并上调RBMS3,且miR-141-3p对相关基因表达及促进癌症发展具有反向作用。过表达MEG3可抑制异种移植瘤生长,通过调节凋亡相关因子促进细胞凋亡,并上调RBMS3表达但下调miR-141-3p。本研究结果表明,MEG3通过miR-141-3p/RBMS3轴抑制BC细胞增殖并促进其凋亡,且MEG3通过miR-141-3p抑制异种移植瘤生长。

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