miR-524-5p reduces the progression of the BRAF inhibitor-resistant melanoma

• Published in: Neoplasia (New York, N.Y.) Vol. 22; no. 12; pp. 789 - 799
• Main Authors: Nguyen, Mai-Huong Thi, Lin, Chen-Huan, Liu, Szu-Mam, Miyashita, Azusa, Ihn, Hironobu, Lin, Hsuan, Ng, Chi Hou, Tsai, Jen-Chieh, Chen, Ming-Hong, Tsai, Mu-Shiun, Lin, In-Yu, Liu, Shu-Chen, Li, Long-Yuan, Fukushima, Satoshi, Lu, Jean, Ma, Nianhan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2020; Neoplasia Press; Elsevier
• Subjects: BRAF inhibitor; Melanoma; miR-524-5p; miRNA; Original article; Resistance; RECIST; STPR; IHC; Melanoma; BRAF inhibitor; LTPR; MITF; CR; Resistance; miR-524-5p; PD; miRNA; IPA; NGS
• ISSN: 1476-5586; 1522-8002; 1476-5586
• DOI: 10.1016/j.neo.2020.10.009

BRAF inhibitors were approved for the treatment of BRAF-mutant melanoma. However, most patients acquire the resistance to BRAF inhibitors after several months of treatment. miR-524-5p is considered as a tumor suppressor in many cancers, including melanoma. In this study, we investigated the biological functions of miR-524-5p in melanoma with acquired resistance to BRAF inhibitor and evaluated the endogenous miR-524-5p expression as a biomarker for melanoma. The results showed that the expression of miR-524-5p was 0.481-fold lower in melanoma tissues (n = 117) than in nevus tissues (n = 40). Overexpression of miR-524-5p significantly reduced proliferative, anchorage-independent growth, migratory and invasive abilities of BRAF inhibitor-resistant melanoma cells. Moreover, the introduction of miR-524-5p led to a reduced development of BRAF inhibitor-resistant melanoma in vivo. Remarkably, the MAPK/ERK signaling pathway was decreased after treatment with miR-524-5p. Furthermore, next-generation sequencing analysis implied that the complement system, leukocyte extravasation, liver X receptor/retinoid-X-receptor activation, and cAMP-mediated signaling may be related to miR-524-5p-induced pathways in the resistant cells. The miR-524-5p level was higher on average in complete response and long-term partial response patients than in progressive disease and short-term partial response patients treated with BRAF inhibitors. Our results proposed that miR-524-5p could be considered as a target for treatment BRAF inhibitor-resistant melanoma and a prognostic marker in the response of patients to BRAF inhibitors for melanoma.