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miR-451a suppresses the development of breast cancer via targeted inhibition of CCND2
Institution:1. Faculty of Medicine, King Mongkut''s Institute of Technology Ladkrabang, Bangkok 10520, Thailand;2. Center of Excellence in Molecular Genetic of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand;3. Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand;4. Omics Sciences and Bioinformatics Center, Chulalongkorn University, Bangkok 10330, Thailand;5. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
Abstract:Extensive research has indicated that miRNAs are crucial for the occurrence and progression of cancers. miR-451a, involved in breast cancer (BC), is one of the miRNAs. This study focused on the mechanism by which miR-451a regulates BC. The levels of miR-451a in BC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan?Meier analysis showed that this was intimately related to the patient's overall survival rate. Functional experiments revealed the negative effects of miR-451a on the abilities of BC cells to multiply (tested by Cell Counting Kit-8), migrate (tested by wound healing assay), and invade (tested by Transwell assay) and its positive effects on apoptosis (tested by flow cytometry). Western blotting indicated that the expression of tumor-related proteins was affected by miR-451a. Moreover, in vivo experiments suggested that tumor growth was clearly restrained by an miR-451a agonist in a xenograft tumor model. Bioinformatic analysis indicated that miR-451a directly targeted Cyclin D2 (CCND2), as demonstrated by the luciferase reporter assay. An opposite change in the level of CCND2 and miR-451a in BC was indicated by qRT-PCR, western blotting, and immunohistochemistry. Subsequently, functional experiments and western blotting analysis confirmed that CCND2 accelerated BC progression, which was regulated by miR-451a. Cumulatively, research on miR-451a may be valuable for BC treatment.
Keywords:miR-451a  Cyclin D2  Breast cancer  Cell function  Tumor growth
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