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

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.

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.

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.

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.