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

Mai Huong Thi Nguyen, Chen Huan Lin, Szu Mam Liu, Azusa Miyashita, Hironobu Ihn, Hsuan Lin, Chi Hou Ng, Jen Chieh Tsai, Ming Hong Chen, Mu Shiun Tsai, In Yu Lin, Shu Chen Liu, Long Yuan Li, Satoshi Fukushima, Jean Lu, Nianhan Ma

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)789-799
Number of pages11
JournalNeoplasia (United States)
Volume22
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • BRAF inhibitor
  • Melanoma
  • miR-524-5p
  • miRNA
  • Resistance

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