Salinomycin Modulates the Expression of mRNAs and miRNAs Related to Stemness in Endometrial Cancer

Abstract

Background: Salinomycin, an ionophore antibiotic, has a strong anti-cancer effect, inducing the apoptosis of cancer cells and cancer stem cells. Objective: The aim of the study was to assess the influence of salinomycin on the expression profile of genes related to stemness and miRNA regulating their expression in endometrial cancer cells. Methods: Endometrial cancer cells of cell line Ishikawa were exposed to salinomycin at concentrations in the range of 0.1- 100 µM, with the aim of determining its pro-apoptotic potential and the concentration which would cause the death of 50% of the cells (Sulforhodamine B test). In the following stages, the cells were incubated with the drug at a concentration of 1µM for 12,24 and 48 hour periods and compared to the control. Determining the changes in the expression of the genes related to stemness and regulating their miRNA was done using the microarray technique and RTqPCR. ELISA assay was performed in order to determining the level of TGFβ2, COL14A1, CDH2, WNT5A in cell culture under salinomycin treatment in comparison to the control. Results: Salinomycin caused the apoptosis of cells. For the concentration of 0.1 µM, a decrease in the population of living cells by 11.9% was determined. For 1 µM, it was 49.8%, for 10 µM -69.4%, and for a concentration of 100 µM - 87.9%. The most noticeable changes in the expression caused by the addition of salinomycin into the culture were noted for mRNA: TGFβ2; WNT5A (up-regulated); COL14A1; CDH2 (down-regulated), as well as miRNA: hsa-miR-411 (up-regulated); hsamiR-200a; hsa-miR-33a; hsa-miR-199a; hsa-miR-371-5p; hsa-miR-374; hsa-miR-374b (down-regulated). Conclusion: It was confirmed that salinomycin has the influence for the stemness process. The most noticeable changes in the expression were noted for mRNA: TGFβ2; COL14A1; CDH2; WNT5A, as well as for miRNA: hsa-miR-200a; hsa-miR33a; hsa-miR-199a; hsa-miR-371-5p; hsa-miR-411; hsa-miR-374a; hsa-miR-374b.

Expression and function of long non-coding RNA DLX6-AS1 in endometrial cancer

“…Most miRs have previously been reported to be deregulated in EC (Donkers et al, 2021). For instance, a reduced level of miR-374 and miR-374a in EC cell lines has been validated (Jayaraman et al, 2017;Talkowski et al, 2021). As for miR-374a-3p, it has been revealed that increased expression of miR-374a-3p contributes to restraining the biological activities of non-small-cell lung cancer cells (NSCLCs), (Yang et al, 2020), while the miR-374a-3p function in EC has remained largely unknown.…”

Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines

“…Conventional treatments such as radiotherapy, chemotherapy, and surgery are common cancer therapy methods, but they often lead to tumour recurrence. This recurrence is mainly because conventional therapies only target the bulk of the tumour, leaving cancer stem cells (CSCs) behind, and they are believed to be the driving force of tumour progression [ 5 , 6 , 7 , 8 ]. CSCs are a subset of a tumour [ 2 , 9 ] as they mimic stem cell features, including active proliferation and the ability to metastasise, self-renew, and differentiate.…”