Drug Design, Development and Therapy (Oct 2019)

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

  • Yu Y,
  • Xiang N,
  • Lin M,
  • Huang JW,
  • Zhang J,
  • Cheng B,
  • Ji C

Journal volume & issue
Vol. Volume 13
pp. 3717 – 3726

Abstract

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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 [email protected] ChengDepartment of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, People’s Republic of ChinaEmail [email protected]: 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

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