Molecules and Cells

  • 제41권2호
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  • Pages.119-126
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  • 2018
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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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)
  • 투고 : 2017.09.22
  • 심사 : 2017.11.24
  • 발행 : 2018.02.28
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초록

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.

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참고문헌

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