Ectopic Expression of Mir-34A/-328 Sensitizes Breast Cancer Stem Cells to Gamma Rays/Doxorubicin by Bcl2/Abcg2 Targeting Publisher Pubmed



Kouhestani SD¹ ; Khalili S² ; Razi A³ ; Aghili M⁴ ; Moghadam MF¹ Show Affiliations
Source: Molecular Biology Reports Published:2025

Abstract

Purpose: In the present study, we aim to identify novel molecular targets for sensitizing Breast cancer stem cells (BCSCs) to common antitumor treatments. MicroRNAs (miRNAs) play key roles in pivotal cellular processes. Therefore, modulating the expression of these miRNAs may lead to increased sensitivity of BCSCs to current treatments or overcome their therapeutic resistance. Due to their pivotal roles in the regulation of apoptosis (via BCL2) and chemoresistance (via ABCG2) and their differential expression in BCSCs (compared to non-BCSCs), miR-34a and miR-328 were selected for analysis. Methods: BCSCs were propagated and characterized. Then, the expression levels of miRNAs, which are associated with treatment resistance (miR-21, -34a, -328, -128, -200c, Let-7i), were quantified in BCSCs and non-BCSCs before and after treatment with doxorubicin (DOX) and radiation. BCSCs were subsequently transduced with recombinant lentiviruses that contained miR-34a or miR-328 to sensitize these cells to DOX- and radio-treatment, respectively. The effects of miR-34a or miR-328 overexpression on apoptosis induction after irradiation or DOX treatment were assessed by flow cytometry analysis. Results: Ectopic expression of miR-34a or miR-328 in BCSCs, respectively, decreased the BCL2 and ABCG2 expression levels compared to untreated cells. Furthermore, overexpression of miR-34a or miR-328 in BCSCs led to increased susceptibility to apoptosis induced by radiation or DOX treatment, respectively. Conclusion: It could be concluded that miR-34a or miR-328 could effectively increase radiation- or DOX-induced cell apoptosis by negatively regulating Bcl-2 or ABCG2 expression levels in BCSCs, respectively. Hence, ectopic expression of these miRNAs could sensitize BCSCs to irradiation and DOX treatment. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.