دورية أكاديمية
N6-methyladenosine-mediated downregulation of miR-374c-5p promotes cadmium-induced cell proliferation and metastasis by targeting GRM3 in breast cancer cells
العنوان: | N6-methyladenosine-mediated downregulation of miR-374c-5p promotes cadmium-induced cell proliferation and metastasis by targeting GRM3 in breast cancer cells |
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المؤلفون: | Yang Yue, Ping Deng, Heng Xiao, Miduo Tan, Hui Wang, Li Tian, Jia Xie, Mengyan Chen, Yan Luo, Liting Wang, Yidan Liang, Huifeng Pi, Zhou Zhou, Zhengping Yu |
المصدر: | Ecotoxicology and Environmental Safety, Vol 229, Iss , Pp 113085- (2022) |
بيانات النشر: | Elsevier, 2022. |
سنة النشر: | 2022 |
المجموعة: | LCC:Environmental pollution LCC:Environmental sciences |
مصطلحات موضوعية: | Breast cancer, Cadmium, MiR-374c-5p, M6A, GRM3, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350 |
الوصف: | Cadmium (Cd) is a toxic heavy metal that can facilitate the development and progression of breast cancer (BC). Emerging evidence has indicated that the progression of Cd-exposed BC is related to the dysregulation of microRNAs (miRNAs). The purpose of our study was to investigate the expression pattern and underlying mechanisms of miR-374c-5p in Cd-mediated BC progression. In this study, T-47D cells and MCF-7 cells were treated with different concentrations of Cd (0.1, 1 and 10 μM) for 72 h. MiR-374c-5p expression was downregulated, and transfection of miR-374c-5p mimics significantly decreased BC cell proliferation, migration and invasion induced by 10 μM Cd. Importantly, we used the Cytoscape software plugin cytoHubba to analyse the intersected genes between our RNA-Seq results and the mirDIP database, and six hub genes (CNR1, CXCR4, GRM3, RTN1, SLC1A6 and ZEB1) were identified as potential direct targets of miR-374c-5p in our model; however, luciferase reporter assays indicated that miR-374c-5p only repressed GRM3 by directly binding to its 3′-untranslated region (UTR). Of note, we verified that suppression of N6-methyladenosine (m6A) modification led to miR-374c-5p downregulation by decreasing its RNA transcript stability. Together, these findings demonstrated that m6A modification of pri-miRNA-374c blocks miRNA-374c-5p maturation and then activates GRM3 expression, which drives BC cell metastasis after Cd exposure. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 0147-6513 |
العلاقة: | http://www.sciencedirect.com/science/article/pii/S0147651321011970Test; https://doaj.org/toc/0147-6513Test |
DOI: | 10.1016/j.ecoenv.2021.113085 |
الوصول الحر: | https://doaj.org/article/371b077a6a8045879b558c946573fc81Test |
رقم الانضمام: | edsdoj.371b077a6a8045879b558c946573fc81 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 01476513 |
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DOI: | 10.1016/j.ecoenv.2021.113085 |