Background: Melanoma is known as the most aggressive and lethal type of cutaneous cancer due to its rapid development of drug resistance to chemotherapy drugs.
Methods: In our study, we conducted a variety of studies, including quantitative PCR, Western blot, and autophagy and apoptosis assays to investigate the involvement of miR-26a and HMGB1 in modulation of dabrafenib sensitivity in human melanoma cell lines.
Results: Our studies revealed that the expressions of miR-26a and HMGB1 were altered in two melanoma cell lines after dabrafenib treatment. Additionally, dabrafenib caused autophagy in melanoma and this autophagic process was regulated by miR-26a via modifying HMGB1 expression. Furthermore, silencing HMGB1-inhibited autophagy induced by dabrafenib in melanoma cells. Last, we verified that treatment with a miR-26a mimic and HMGB1 shRNA could increase the efficacy of dabrafenib in melanoma cells.
Conclusion: Taken together, we showed that miR-26a is involved in the regulation of dabrafenib efficacy via a HMGB1-dependent autophagy pathway in melanoma cells. These results shed light on a novel treatment for conventional dabrafenib-based chemotherapy for melanoma.
Keywords: melanoma, miR-26a, HMGB1, dabrafenib, autophagy, apoptosis