MiR-18a-5p attenuates HER2-positive breast cancer development by regulating PI3K/AKT pathway

• Published in: Cancer biology & therapy 2023-12, Vol.24 (1), p.2224512-2224512
• Main Authors: Liu, Yongjun, Yang, Hua
• Format: Article
• Language: English
• Subjects: Breast cancer; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation; Female; HER2; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-18a-5p; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT pathway; Proto-Oncogene Proteins c-akt - metabolism; Research Paper
• ISSN: 1538-4047; 1555-8576
• DOI: 10.1080/15384047.2023.2224512

Objective: Human epidermal growth factor receptor 2 positive (HER2 + ) breast cancer (BC) is associated with poor prognosis. This study aimed to elucidate the role of miR−18a−5p in regulation of HER2 + -BC progression along with its mechanism of action. Methods: The expression of miR−18a−5p and HER2 in BC cells and tissues was analyzed using quantitative real-time PCR while protein level expression of AKT Serine/Threonine Kinase 1 (AKT), phosphorylated AKT (p-AKT), Phosphatidylinositol 3-kinase (PI3K), phosphorylated-PI3K (p-PI3K), and HER2 were assessed by western blotting. Cell Counting Kit−8, wound healing, and cell adhesion assays were used for in vitro analysis along with xenograft tumor model construction for in vivo analysis. Pearson correlation analysis and dual-luciferase reporter (DLR) assays were used to ascertain the targeting association between miR−18a−5p and HER2. Results: There was a downregulation of miR−18a−5p expression in the BC tissues and cells. Functionally, overexpression of miR−18a−5p prevented BC cells from proliferation, adherence, migration, and activation of the P-PI3K/P-AKT pathway. In vivo experiment revealed that tumor growth was suppressed when miR−18a−5p was overexpressed. In BC, HER2 overexpression increased cell proliferation, cell-cell adhesion, migration, and P-PI3K/P-AKT signaling, but overexpression of miR−18a−5p reversed this effect because of the target relationship between miR−18a−5p and HER2. Conclusion: miR−18a−5p inhibits HER2 + BC progression by targeting HER2 to inhibit PI3K/AKT pathway activation. A theoretical foundation for the identification of new therapeutic targets for HER2 + BC may be provided by the miR−18a−5p - HER2 axis.