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

• Main Authors: Yu Y, Xiang N, Lin M, Huang JW, Zhang J, Cheng B, Ji C
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-10-01
• Series: Drug Design, Development and Therapy
• Subjects: melanoma; mir-26a; hmgb1; dabrafenib; autophagy; apoptosis
• Online Access: https://www.dovepress.com/mir--26a-sensitizes-melanoma-cells-to-dabrafenib-via-targeting-hmgb1-d-peer-reviewed-article-DDDT

Yan Yu,1,* Niu Xiang,2,* Min Lin,2 Jin-Wen Huang,2 Jing Zhang,2 Bo Cheng,2 Chao Ji2 1Department of Dermatology, First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao JiDepartment of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, People’s Republic of ChinaEmail [e-mail] ChengDepartment of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, People’s Republic of ChinaEmail [e-mail]: 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