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01 March 2019 : Animal Research  

Methylation-Mediated Silencing of MicroRNA-211 Decreases the Sensitivity of Melanoma Cells to Cisplatin

Ning Li1ABCEF*, Ying Liu1B, Hao Pang1C, Daeshin Lee1D, Yongting Zhou1D, Zhibo Xiao1AEFG

DOI: 10.12659/MSM.911862

Med Sci Monit 2019; 25:1590-1599

Abstract

BACKGROUND: Malignant melanoma is recalcitrant to most existing chemotherapies, and aberrant expression of miR-211 plays prominent roles in progression of melanoma. However, the trigger mechanism of aberrant miR-211 expression in melanoma is still elusive.

MATERIAL AND METHODS: We used qRT-PCR to test miR-211 expression. Cell viability assay and mouse xenograft assay were performed to examine the role of miR-211 on the sensitivity of melanoma cells to cisplatin. The epigenetic modification of miR-211 promoter was assess by DNA methylation analysis and DAC treatment.

RESULTS: In this study, decreased miR-211 expression was detected. Bisulfite sequencing PCR showed that DNA hypermethylation contributed to the downregulation of miR-211 in melanoma tissues. In melanoma cells, overexpressed 211 could enhance the anticancer effect of cisplatin and restoration of miR-211 rendered susceptibility to cisplatin in cisplatin-resistant cells. And the same result was showed in vivo by mouse xenograft assay. What is more, DAC treatment could increase miR-211 expression and EZH2 expression was increased in cisplatin-resistant cells. MiR-211 could be transcriptionally repressed by EZH2 mediated promoter methylation.

CONCLUSIONS: Taken together, our findings revealed that epigenetic modification of miR-211 governed melanoma cell chemosensitivity and were involved in the progression of tumorigenesis.

Keywords: Abnormalities, Drug-Induced, Epigenomics, Apoptosis, Cell Proliferation, Cell Survival, Cisplatin, DNA Methylation, Drug Resistance, Neoplasm, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Gene Silencing, Melanoma, MicroRNAs, Skin Neoplasms, Xenograft Model Antitumor Assays

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Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937676

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750