Background:Dacarbazine 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).
Methods:The 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.
Results:miR-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.
Conclusions:The 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.
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- 凋亡试剂盒
Annexin V-FITC/PI Apoptosis Kit(适用于除C6以外的流式细胞仪)
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