Turkish Journal of Biology
Abstract
Background/aim: Metformin is commonly used to manage type 2 diabetes (T2D) and is being investigated for its potential antiproliferative effects in cancer, particularly in patients with both T2D and malignancies. Drug resistance can develop with any therapeutic agent, and metformin is no exception. As we showed in our previous study, metformin-resistant MDA-MB-468 (MET-R) cells exhibited an EMT-like phenotype. Many transcription factors, as well as miRNAs, can contribute to this altered phenotype. Our current study identifies the contribution of hsa-miR-26a-5p expression to the previously observed phenotype. Materials and methods: By utilizing bioinformatic tools, we identified hsa-miR-26a-5p, whose expression was significantly altered with increasing concentrations of metformin in MET-R cells. We rescued hsa-miR-26a-5p expression and examined the EMT phenotype and apoptotic markers via Western blot analysis. Results: We observed a reduction in hsa-miR-26a-5p expression in response to increasing concentrations of metformin in MET-R cells. Upon successful restoration of hsa-miR-26a-5p expression, a subsequent decrease in the proliferation rate was noted. Moreover, when combined with a PI3K inhibitor, we observed increased sensitivity to the PI3K inhibitor. The EMT and apoptotic markers also tended to decrease upon combinatorial treatment. Conclusion: In this study, we rescued the diminished expression of hsa-miR-26a-5p in MET-R cells to increase the sensitivity to PI3K inhibitor. The combination of a PI3K inhibitor and rescued hsa-miR-26-5p expression resulted in the restoration of the EMT phenotype and proliferation in these cells.
Author ORCID Identifier
ŞAHİKA CINGIR KÖKER: 0000-0002-8529-4532
SENEM NOYAN: 0000-0001-6455-3702
BANU YALÇIN: 0009-0006-5483-7780
İREM DOĞAN TURAÇLI: 0000-0002-3791-3538
DOI
10.55730/1300-0152.2749
Keywords
Triple negative breast cancer, metformin, microRNA, PI3K inhibitor, cell migration, hsa-miR-26a-5p
First Page
336
Last Page
346
Publisher
The Scientific and Technological Research Council of Türkiye (TÜBİTAK)
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
CINGIR KÖKER, Ş, NOYAN, S, YALÇIN, B, & DOĞAN TURAÇLI, İ (2025). The effects of hsa-mir-26a-5p on cell proliferation, migration, and PI3K inhibitor sensitivity in metformin-resistant triple negative breast cancer cells. Turkish Journal of Biology 49 (3): 336-346. https://doi.org/10.55730/1300-0152.2749
