Graduate Student Texas Tech University Health Sciences Center, Lubbock Lubbock, Texas, United States
Introduction/Rationale: Despite advances in treatment, invasive breast cancer remains among the deadliest cancers in women, driven by limited therapeutic options that precisely target their molecular drivers. Mirtrons, an emerging class of intron-derived microRNAs, may represent unrecognized regulators of tumor progression and invasion. This study examines how mirtron-5010 influences cancer stemness and iron accumulation in triple negative MDA-MB-231 breast cancer.
Methods: MDA-MB-231 bulk and stem cell populations were engineered to upregulate mirtron-5010. Classical stemness markers (SOX2, OCT4, NANOG, and KLF4) as well as the regulatory subunit PPP2R2D, were analyzed using quantitative PCR and immunohistochemistry. Intracellular iron levels were measured using FerroOrange fluorescence quantification.
Results: Across bulk cultures, mirtron-5010 upregulation elevated SOX2, OCT4, and NANOG expression, indicating enhanced stem-like characteristics. When looking into tumor stem cell population, mirtron-5010 upregulation further increased SOX2 and NANOG expression. Consistent with this, both bulk and tumor stem cells with mirtron-5010 upregulation showed greater labile iron pool determined by FerroOrange fluorescence, signifying an altered preference in iron metabolic pathways than controls. Interestingly, the subunit PPP2R2D of the PP2A enzyme complex was downregulated in mirtron-5010 upregulated cells.
Conclusion: In conclusion, mirtron-5010 enhances stemness and promotes iron accumulation in invasive breast cancer cells, highlighting its potential as a molecular target for therapy-resistant subtypes. Through modulation of the PP2A enzyme complex, mirtron-5010 also dampens IL-2–driven T-cell activation and proliferation, suggesting a role in shaping the tumor immune microenvironment. Future studies will further delineate the functional consequences of mirtron-5010 expression in both cancer and immune cell contexts across diverse breast cancer models.
