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Open AccessArticle

Metformin Treatment Suppresses Melanoma Cell Growth and Motility Through Modulation of microRNA Expression

by Hui-Wen Tseng 1,2, Sung-Chou Li 3 and Kuo-Wang Tsai 2,4,5,*
Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
Genomics & Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
Department of Chemical Biology, National Pingtung University of Education, Pingtung 90004, Taiwan
Author to whom correspondence should be addressed.
Cancers 2019, 11(2), 209;
Received: 15 January 2019 / Revised: 2 February 2019 / Accepted: 5 February 2019 / Published: 11 February 2019
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
Melanoma is a highly aggressive cancer with high mortality in advanced stages.
Metformin is an oral biguanide drug used for diabetes and has demonstrated positive effects on
cancer prevention and treatment. Herein, we found that metformin significantly suppressed
melanoma cancer cell motility and growth through inducing cell cycle arrest at the G2/M phase and
promoting cell apoptosis. Using the next-generation sequencing approach, we identified three
upregulated microRNAs (miRNA; miR-192-5p, miR-584-3p, and miR-1246) in melanoma cells
treated with metformin. Among these, we examined the roles of miR-192-5p and miR-584-3p and
discovered that they significantly suppressed melanoma cell motility. Furthermore, they inhibited
melanoma cell growth through destroying cell cycle progression and inducing cell apoptosis. Using
microarray and bioinformatics approaches for identifying putative target genes, Epidermal growth
factor (EGF) containing fibulin-like extracellular matrix protein 1 (EFEMP1) gene for miR-192-5p
and an isoform of the secretory carrier membrane proteins (SCAMP3) gene for miR-584-3p could be
silenced through targeting their 3′UTR region directly. EFEMP1 and SCAMP3 knockdown
significantly suppressed melanoma cell growth, but only EFEMP1 knockdown inhibited its motility
abilities. Our findings indicated that miR-192-5p and miR-584-3p might contribute to metformininduced
growth and motility suppression in melanoma cells through silencing their target genes
EFEMP1 and SCAMP3. View Full-Text
Keywords: metformin; miR-192-5p; miR-584-3p; migration; melanoma metformin; miR-192-5p; miR-584-3p; migration; melanoma
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MDPI and ACS Style

Tseng, H.-W.; Li, S.-C.; Tsai, K.-W. Metformin Treatment Suppresses Melanoma Cell Growth and Motility Through Modulation of microRNA Expression. Cancers 2019, 11, 209.

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