miR- 26a Sensitizes Melanoma Cells To Dabrafenib Via Targeting HMGB1-Dependent Autophagy Pathways

• Published in: Drug design, development and therapy development and therapy, 2019-01, Vol.13, p.3717-3726
• Main Authors: Yu, Yan, Xiang, Niu, Lin, Min, Huang, Jin-Wen, Zhang, Jing, Cheng, Bo, Ji, Chao
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Autophagy; Autophagy - drug effects; Biotechnology; Breast cancer; Cancer therapies; Cell adhesion & migration; Cell growth; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; dabrafenib; Dermatology; Dose-Response Relationship, Drug; Drug development; Drug resistance; Drug Screening Assays, Antitumor; Gene expression; hmgb1; HMGB1 protein; HMGB1 Protein - metabolism; Hospitals; Humans; Imidazoles - pharmacology; Immunoglobulins; Kinases; Medical prognosis; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; MicroRNAs; MicroRNAs - genetics; mir-26a; Molecular Structure; Mutation; Original Research; Oximes - pharmacology; Phagocytosis; Proteins; Structure-Activity Relationship; Tumor Cells, Cultured; Tumorigenesis
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S225671

Melanoma is known as the most aggressive and lethal type of cutaneous cancer due to its rapid development of drug resistance to chemotherapy drugs. 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. 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. 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.