长链非编码RNA MEG3通过调控miR-330/CNN1在乳腺癌中发挥抑制作用。

Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1.

作者信息

Yi Dandan, Wang Zetian, Yang Haojie, Wang Ru, Shi Xianbiao, Liu Zhijian, Xu Fazhan, Lu Qing, Chu Xiao, Sang Jianfeng

机构信息

Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.

Department of Trauma-Emergency and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, China.

出版信息

Aging (Albany NY). 2024 Jan 17;16(2):1318-1335. doi: 10.18632/aging.205419.

DOI:10.18632/aging.205419

PMID:38240701

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10866439/

Abstract

BACKGROUND

The current study aimed to investigate the molecular mechanism of long non-coding RNA (lncRNA) MEG3 in the development of breast cancer.

METHODS

The regulating relationships among lncRNA MEG3, miRNA-330 and CNN1 were predicted by bioinformatics analysis of breast cancer samples in the Cancer Genome Atlas database. The differential expression of lncRNA MEG3, miRNA-330 and CNN1 was first validated in breast cancer tissues and cells. The effects of lncRNA MEG3 on breast cancer malignant properties were evaluated by manipulating its expression in MCF-7 and BT-474 cells. Rescue experiments, dual-luciferase assays, and RNA immunoprecipitation (RIP) experiments were further used to validate the relationships among lncRNA MEG3, miRNA-330 and CNN1.

RESULTS

Bioinformatics analysis showed that lncRNA MEGs and CNN1 were significantly downregulated in breast cancer tissues, while miR-330 was upregulated. These differential expressions were further validated in our cohort of breast cancer samples. High expression levels of lncRNA MEG3 and CNN1 as well as low expression of miR-330 were significantly associated with favorable overall survival. Overexpression of lncRNA MEG3 significantly inhibited cell viability, migration and invasion, decreased cells in S stage and promoted cell apoptosis. Dual-luciferase reporter gene assay and RIP experiments showed that lncRNA MEG3 could directly bind to miR-330. Moreover, miR-330 mimics on the basis of lncRNA MEG3 overexpression ameliorated the tumor-suppressing effects of lncRNA MEG3 in breast cancer malignant properties by decreasing CNN1 expression.

CONCLUSION

Our study indicated lncRNA MEG3 is a breast cancer suppressor by regulating miR-330/CNN1 axis.

摘要

背景

本研究旨在探讨长链非编码RNA（lncRNA）MEG3在乳腺癌发生发展中的分子机制。

方法

通过对癌症基因组图谱数据库中乳腺癌样本进行生物信息学分析，预测lncRNA MEG3、miRNA - 330和CNN1之间的调控关系。首先在乳腺癌组织和细胞中验证lncRNA MEG3、miRNA - 330和CNN1的差异表达。通过调控MCF - 7和BT - 474细胞中lncRNA MEG3的表达，评估其对乳腺癌恶性生物学特性的影响。进一步通过挽救实验、双荧光素酶报告基因检测和RNA免疫沉淀（RIP）实验，验证lncRNA MEG3、miRNA - 330和CNN1之间的关系。

结果

生物信息学分析显示，lncRNA MEG3和CNN1在乳腺癌组织中显著下调，而miR - 330上调。这些差异表达在我们的乳腺癌样本队列中得到进一步验证。lncRNA MEG3和CNN1的高表达以及miR - 330的低表达与良好的总生存期显著相关。lncRNA MEG3的过表达显著抑制细胞活力、迁移和侵袭，减少S期细胞数量并促进细胞凋亡。双荧光素酶报告基因检测和RIP实验表明，lncRNA MEG3可直接与miR - 330结合。此外，基于lncRNA MEG3过表达的miR - 330模拟物通过降低CNN1表达，改善了lncRNA MEG3对乳腺癌恶性生物学特性的抑制作用。