通过直接靶向TMEM41B抑制微小RNA-660-5p可降低乳腺癌进展。
Inhibition of microRNA-660-5p decreases breast cancer progression through direct targeting of TMEM41B.
作者信息
Villarreal-García Valeria, Estupiñan-Jiménez José Roberto, Gonzalez-Villasana Vianey, Vivas-Mejía Pablo E, Flores-Colón Marienid, Ancira-Moreno Irma Estefanía, Zapata-Morín Patricio Adrián, Altamirano-Torres Claudia, Vázquez-Guillen José Manuel, Rodríguez-Padilla Cristina, Bayraktar Recep, Rashed Mohamed H, Ivan Cristina, Lopez-Berestein Gabriel, Reséndez-Pérez Diana
机构信息
Facultad de Ciencias Biológicas, Departamento de Biología Celular y Genética, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.
Department of Biochemistry, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico.
出版信息
Hereditas. 2024 Dec 21;161(1):53. doi: 10.1186/s41065-024-00357-5.
BACKGROUND
Breast cancer is the most prevalent cancer among women worldwide. Most breast cancer-related deaths result from metastasis and drug resistance. Novel therapies are imperative for targeting metastatic and drug-resistant breast cancer cells. Accumulating evidence suggests that dysregulated microRNAs (miRNAs) promote breast cancer progression, metastasis, and drug resistance. Compared with healthy breast tissue, miR-660-5p is notably overexpressed in breast cancer tumor tissues. However, the downstream effectors of miR-660-5p in breast cancer cells have not been fully elucidated. Our aim was to investigate the role of miR-660-5p in breast cancer cell proliferation, migration, invasion, and angiogenesis and to identify its potential targets.
RESULTS
Our findings revealed significant upregulation of miR-660-5p in MDA-MB-231 and MCF-7 cells compared with MCF-10 A cells. Furthermore, inhibiting miR-660-5p led to notable decreases in the proliferation, migration, and invasion of breast cancer cells, as well as angiogenesis, in HUVEC cells. Through bioinformatics analysis, we identified 15 potential targets of miR-660-5p. We validated TMEM41B as a direct target of miR-660-5p via Western blot and dual-luciferase reporter assays.
CONCLUSIONS
Our study highlights the upregulation and involvement of miR-660-5p in breast cancer cell proliferation, migration, invasion, and angiogenesis. Additionally, we identified TMEM41B as a direct target of miR-660-5p in breast cancer cells.
背景
乳腺癌是全球女性中最常见的癌症。大多数与乳腺癌相关的死亡是由转移和耐药性导致的。针对转移性和耐药性乳腺癌细胞的新型疗法势在必行。越来越多的证据表明，失调的微小RNA（miRNA）促进乳腺癌的进展、转移和耐药性。与健康乳腺组织相比，miR-660-5p在乳腺癌肿瘤组织中显著过表达。然而，miR-660-5p在乳腺癌细胞中的下游效应因子尚未完全阐明。我们的目的是研究miR-660-5p在乳腺癌细胞增殖、迁移、侵袭和血管生成中的作用，并确定其潜在靶点。
结果
我们的研究结果显示，与MCF-10 A细胞相比，MDA-MB-231和MCF-7细胞中miR-660-5p显著上调。此外，抑制miR-660-5p导致乳腺癌细胞的增殖、迁移和侵袭以及人脐静脉内皮细胞（HUVEC）中的血管生成显著减少。通过生物信息学分析，我们确定了miR-660-5p的15个潜在靶点。我们通过蛋白质免疫印迹法和双荧光素酶报告基因检测验证了跨膜蛋白41B（TMEM41B）是miR-660-5p的直接靶点。
结论
我们的研究强调了miR-660-5p在乳腺癌细胞增殖、迁移、侵袭和血管生成中的上调及参与作用。此外，我们确定TMEM41B是乳腺癌细胞中miR-660-5p的直接靶点。
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