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http://dx.doi.org/10.14348/molcells.2018.2235

Overexpression of microRNA-612 Restrains the Growth, Invasion, and Tumorigenesis of Melanoma Cells by Targeting Espin  

Zhu, Ying (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University)
Zhang, Hao-liang (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University)
Wang, Qi-ying (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University)
Chen, Min-jing (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University)
Liu, Lin-bo (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University)
Publication Information
Molecules and Cells / v.41, no.2, 2018 , pp. 119-126 More about this Journal
Abstract
microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.
Keywords
aggressiveness; downregulation; metastasis; microRNA; target;
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