AC104024.2/miR-30a-5p Axis Regulates Malignant Progression of Breast Cancer Through a Depression-Related Gene, MAP2K3

Breast cancer (BC), a malignant tumor, is characterized by high incidence and poor prognosis among women worldwide. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) can regulate the initiation and progression of BC through competitive endogenous RNA (ceRNA) mechanisms. Despite depression being an important factor affecting patients with BC, the ceRNA regulatory network involving depression-related genes in BC remains unclear.

In this study, we explored the role of the AC104024.2/miR-30a-5p axis in BC progression by targeting the depression-related gene mitogen-activated protein kinase kinase 3 (MAP2K3). We used depression-like mouse models to confirm the role of MAP2K3 in modulating depressive behavior. Additionally, gene set enrichment analyses (GSEA) and phenotypic experiments were conducted to verify the effects of the AC104024.2/miR-30a-5p/MAP2K3 axis on BC cell proliferation, migration, and apoptosis. Luciferase reporter assays were performed to demonstrate the ceRNA function of AC104024.2 for miR-30a-5p.

Our results showed that the AC104024.2/miR-30a-5p axis promotes the malignant progression of BC by regulating MAP2K3. In depression-like mouse models, MAP2K3 was identified as a key gene modulating depressive behavior. The AC104024.2/miR-30a-5p/MAP2K3 axis significantly influenced BC cell proliferation, migration, and apoptosis. Luciferase reporter assays confirmed that AC104024.2 acts as a ceRNA for miR-30a-5p, thereby affecting MAP2K3 expression. Rescue experiments suggested that the regulatory effects of AC104024.2 on BC malignancy are at least partly dependent on MAP2K3.

This study uncovered the role of the depression-related ceRNA network in BC progression and identified AC104024.2 and MAP2K3 as potential biomarkers for the diagnosis and treatment of BC. These findings provide significant clinical implications and applications for the management of BC.