MicroRNA-153-3p sensitizes melanoma cells to dacarbazine by suppressing ATG5-mediated autophagy and apoptosis.

backgroundDacarbazine is one of the most commonly used chemotherapeutic agents for the treatment of melanoma; however, only 5-10% of patients benefit from this treatment. MicroRNA-153-3p (miR-153-3p) has a tumor-suppressive effect in melanoma. In the present study, we found that miR-153-3p was downregulated in melanoma cell lines (A357 and M14).

methodsThe target relationship between miR-153-3p and Autophagy-related gene 5 (ATG5) was confirmed by Dual-Luciferase Reporter Assay. Cell Counting Kit-8, flow cytometry, immunofluorescence, and Western blot were used to examine cell viability, apoptosis, and autophagy, respectively.

resultsmiR-153-3p overexpression decreased the half-maximal inhibitory concentration value of dacarbazine, while increasing the apoptotic rate in both A357 and M14 cells. Moreover, miR-153-3p enhanced dacarbazine-induced autophagy in melanoma cells. Our bioinformatics study revealed that ATG5 is one of the potential targets of miR-153-3p. The overexpression of ATG5 decreased dacarbazine sensitivity and promoted proliferation, as well as inhibited apoptosis and autophagy in melanoma cells. miR-153-3p exhibited suppressive effects via directly binding and downregulating ATG5 expression, which subsequently increased sensitivity to dacarbazine and inhibited proliferation, and enhanced apoptosis and autophagy in melanoma cells.

conclusionsThe results of the present study showed that miR-153-3p sensitizes melanoma cells to dacarbazine by suppressing ATG5-mediated autophagy and apoptosis, and provided a basis to explore the functions of miRNAs on drug resistance in the treatment of melanoma.