MiR-409-3p/Rab10/BRCA1 axis inhibits malignant transformation of endometrial carcinoma

Abstract

Background

Current research suggests that miR-409-3p plays the role of a tumor suppressor by regulating key oncogenes, but its mechanism in endometrial carcinoma (EC) remains unclear.

Objectives

This study evaluated how miR-409-3p functions in inhibiting the malignant transformation of EC by targeting ras-related protein Rab-1 (Rab10) and exploring its impact on breast cancer susceptibility gene 1 (BRCA1) expression.

Materials and methods

Experiments were performed in RL95-2 and HEC-1B EC cell lines and normal endometrial stromal cells (ESCs). miR-409-3p expression was manipulated using lentiviral vectors. CCK-8 assays assessed cell proliferation, Transwell assays measured invasion, real-time PCR and Western blot analyzed gene expression. Flow cytometry evaluated cell cycle changes. Malondialdehyde (MDA) and superoxide dismutase (SOD) assays were used to assess oxidative stress levels.

Results

MiR-409-3p upregulation reduced Rab10 expression by 2.5-fold (P < 0.001) and increased BRCA1 levels by 1.8-fold (P < 0.01), inhibiting EC cell expansion and invasion (P < 0.05). Further, BRCA1 upregulation was reversed by Rab10 overexpression (P < 0.05). BRCA1 upregulation induced cell cycle arrest and alleviated oxidative stress, suggesting a protective role (P < 0.05). Knockdown of BRCA1 reversed the anticancer impact of miR-409-3p/Rab10 signaling (P < 0.05), confirming its critical role in the pathway.

Conclusion

This study is the first to demonstrate that miR-409-3p suppresses EC malignancy via Rab10-mediated BRCA1 upregulation, revealing a novel therapeutic axis for EC. These findings highlight miR-409-3p as a potential therapeutic target and implications for future research and clinical applications in gynecological cancer treatment.