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Research Paper|Volume 16, Issue 2|pp 1318—1335

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

Dandan Yi1, Zetian Wang2, Haojie Yang3, Ru Wang1, Xianbiao Shi1, Zhijian Liu1, Fazhan Xu4, Qing Lu5, Xiao Chu6, Jianfeng Sang1
  • 1Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China
  • 2Department of Trauma-Emergency and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, China
  • 3Department of Coloproctology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
  • 4Department of General Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China
  • 5Department of Breast Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
  • 6Department of Thoracic Surgery, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China
* Co-first authors
Received: July 7, 2023Accepted: November 10, 2023Published: January 17, 2024
https://doi.org/10.18632/aging.205419

Copyright: © 2024 Yi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.