In silico analysis of the association of hsa-miR-16 expression and cell survival in MDA-MB-231 breast cancer cells subjected to photodynamic therapy

Background: Breast cancer is the most common malignancy effecting women, and the triple-negative breast cancer (TNBC) subtype is particularly aggressive. This study aimed to evaluate the differential expression pattern of microRNAs (miRNAs) between untreated MDA-MB-231 cells (TNBC cell model) and those that survived photodynamic therapy (PDT) to gain insights into cell survival mechanisms. Methods: Two PDT cycles were applied to MDA-MB-231 cells, using delta-aminolevulinic acid (ALA) followed by laser light at 635 nm. RNA was obtained from cells surviving PDT and untreated cells. The miRNAs expression profile was analyzed to detect the differences between the two groups. The potential target network of hsa-miR-16 was examined in silico with the integrative database Ingenuity (R) Pathway Analysis software. Results: After the first and second PDT cycles, 17.8% and 49.6% of the MDA-MB-231 cells were viable. Micro array profiling of miRNAs showed decreased hsa-miR-16 expression (p < 0.05) in MDA-MB-231 cells surviving PDT when compared to the control cells. The predicted downstream targets of hsa-miR-16 were: 1) tumor suppressor protein 53; 2) molecules related to the cell cycle, such as cyclin D1, D3, and E1, and checkpoint kinase 1; 3) cell proliferation molecules, including fibroblast growth factor 1, 2 and 7 and fibroblast growth factor receptor 1; and 4) apoptosis-related molecules, consisting of BCL-2, B-cell leukemia/lymphoma 2, caspase 3, and cytochrome c. Conclusions: The differential expression of hsa-miR-16 between untreated MDA-MB-231 cells and those surviving PDT has not been previously reported. There was a lower expression of hsa-miR-16 in treated cells, which probably altered its downstream target network. In silico analysis predicted, a network related to the cell cycle, proliferation and apoptosis. These results are congruent with previous descriptions of hsa-miR-16 as a tumor suppressor and suggest that the treated population has increased their capacity to survive.

Automated summary

This study compared the differential expression of microRNAs between untreated MDA-MB-231 cells and those surviving photodynamic therapy (PDT). The results showed a significant decrease in hsa-miR-16 expression in cells surviving PDT, which may have altered its downstream target network. Analysis also predicted a network related to cell cycle, proliferation, and apoptosis, suggesting an enhanced survival capacity in the treated population.