miR-145-5p Inhibits HER2-Positive Breast Cancer Cells via Targeting ARF6

Lixian Yang,1 Wei Dang,2 Fanting Kong,1 Xuan Zhang,1 Lei Zheng,1 Lining Jia,1 Xiaowei Li,1 Na Lu1 1Department of Breast Surgery, Xingtai People’s Hospital, Xingtai, Hebei Province, 054000, People’s Republic of China; 2Medical Research Center, Xingtai Medical College, Xingtai, Hebei Province, 054000, People’s Republic of ChinaCorrespondence: Lixian Yang, Department of Breast Surgery, Xingtai People’s Hospital, Xingtai, Hebei Province, People’s Republic of China, Email [email protected]: The objective of this study was to examine how miR-145-5p contributes to inhibiting the growth and movement of breast cancer cells by targeting and modulating the ADP-ribosylation factor 6 gene, as well as to clarify the mechanisms involved.Methods: Bioinformatics analysis was used to study miR-145-5p expression in breast cancer samples from the TCGA database. RT-qPCR was performed on 25 pairs of HER2-positive breast cancer tissues and adjacent normal tissues, as well as in SK-BR3 and MCF10A cell lines. The effects of miR-145-5p overexpression on cell viability, migration, and invasion were assessed using CCK-8, scratch, and Transwell assays in SK-BR3 cells. A dual luciferase reporter assay was used to confirm miR-145-5p binding to the 3’-UTR of ARF6 mRNA. Additionally, the combined effects of miR-145-5p and ARF6 overexpression on SK-BR3 cell proliferation, migration, and invasion were evaluated.Results: The examination of the TCGA database indicated that the expression levels of miR-145-5p were reduced in both paired and unpaired breast cancer tissues in comparison to normal control breast tissues. Notably, miR-145-5p showed a remarkably lower expression in HER2-positive breast cancer tissues versus paraneoplastic tissues. When the cells were transfected with a miR-145-5p mimic, there was a significant reduction in SK-BR3 cell proliferation, migration, and invasion in vitro. Conversely, the transfection of the cells with a miR-145-5p inhibitor led to a notable increase in SK-BR3 cell proliferation, migration, and invasion. Furthermore, miR-145-5p was found to suppress the expression of ARF6 mRNA by directly interacting with its 3’-untranslated region.Conclusion: Overall, this study reveals that miR-145-5p suppresses the proliferation, migration, and invasion of breast cancer cells by interacting with ARF6 mRNA. Consequently, this miRNA might serve as a new target for accurate diagnosis and treatment of breast cancer.Keywords: miR-145, ARF6, breast cancer, HER2-positive