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

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/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.

EZH2 promotes the expression of LPA1 by mediating microRNA-139 promoter methylation to accelerate the development of ovarian cancer

“…An existing study identified the ability of EZH2 to repress miR-708 expression by incorporating promoter methylation in the glioma tissues and cells [29]. Likewise, the miR-211 expression was reduced by EZH2-mediated methylation in malignant melanoma [7], and overexpression of EZH2 significantly decreased miR-193a expression in OC [30], which was in compliance with the observed mechanism of EZH2-mediated methylation in our study. Our findings elicited that EZH2 could downregulate the miR-139 expression by engaging H3K27me3 to stimulate the methylation of miR-139 promoter, as proved by the ChIP assay.…”

“…An existing study unraveled that EZH2 played a crucial role in the development of OC [ 6 ]. EZH2 was also reported to affect tumorigenesis by mediating the methylation of microRNA (miR)-211 [ 7 ]. Besides, EZH2 was validated to meditate and influence the insulin-like growth factor 1 receptor by direct transcriptional suppression of miR-139 [ 8 ].…”

The Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers

“…Thus, the EZH2/DNMT1/MIR211/RAB22A axis might provide novel insights into the molecular pathogenesis of both melanoma and glioblastoma, particularly on the EMT processes in these two different cancers. In a separate study, Li N et al reported that the silencing of MIR211 expression by methylation is associated with reduced cisplatin sensitivity in melanoma ( 39 ). This observation, however, may be interpreted as an indirect consequence of reduced EMT in MIR211 deficient cells, because increased EMT increases the resistance of cells to cisplatin ( 40 ).…”

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

“…Besides genetic variations, epigenetic changes or post-transcriptional modifications of miRNAs can lead to deregulated expression in tumor cells [255]. For example, DNA hypermethylation can initiate the downregulation of miR-211 in melanoma tissue, which is a tumor-suppressive miRNA and suppressed in melanoma [256]. In HCC, numerous tumor-suppressive miRNAs including miR-1, miR-124 and miR-203 are downregulated during hepatocarcinogenesis as a result of promoter hypermethylation [257].…”