microRNA‐21 is upregulated in malignant melanoma and influences apoptosis of melanocytic cells

Abstract

Overexpression of microRNA-21 (miR-21) has been observed in various cancer types, but little is known about the role of miR-21 in melanoma. In this study, we demonstrate that levels of miR-21 are significantly increased in primary melanoma tissues as compared to benign nevi and in human melanoma cell lines as compared to melanocytic cell preparations. We show that downregulation of miR-21 in melanoma cell lines with high endogenous miR-21 expression induced apoptosis, whereas proliferation was not significantly altered. Upregulation of miR-21 in melanocytes resulted in increased proliferation and decreased apoptosis. However, in the MEWO melanoma cells with low endogenous miR-21 expression, upregulation of miR-21 had no functional effects. These findings indicate a potential pathogenetic role of miR-21 upregulation in a subgroup of melanomas.

miR-339-3p Is a Tumor Suppressor in Melanoma

“…Notably, miRNAs miR-21 (22), and miR-214 (23) previously reported as miRNAs promoting cancer cell invasion could be confirmed in our functional miRNA screening approach ( Fig. 1A and B).…”

microRNA-10b is a prognostic biomarker for melanoma

“…We then sought to verify the prognostic value of miR-21, the miR200 family, and miR-205 because these had been studied by us using independent samples previously and also by others. [14][15][16][17][18][19][20][21][22][23][24][25][26] We demonstrate that miR-10b and miR-200b have independent prognostic value in a multivariable logistic regression model, raising the possibility that a miRNA panel could be used to better stratify melanoma patients than AJCC staging alone. Absence of Breslow thickness as an independent prognostic factor from the final multivariable model may reflect the fact that all of these melanomas were relatively thick, suggesting that miRNA expression may have prognostic value in this high-risk melanoma subset.…”

“…Given the large number of candidate miRNAs in the published literature, we focused on a small group of candidates that were relevant to studies published from our own laboratories. Specifically, we assessed miR-21 because we have previously analyzed this in blood 14 and other groups have found it to be relevant to melanoma, [15][16][17][18][19] and the miR200 family and mir205 because they influence EMT master regulators, about which we 20 and others [21][22][23][24][25][26] have previously published. Because these miRNAs had been previously discovered as melanoma prognostic biomarker candidates in independent experiments with different case sets, we combined the training and validation sets from the current study, and then analyzed these miRNAs in individual samples.…”

Major apoptotic mechanisms and genes involved in apoptosis

“…miR-24 regulates apoptosis by binding to coding sequence of Fas-associated factor 1 (FAF1) mRNA and induced apoptosis of several different types of cancer [166]. miR-21 also negatively regulates PTEN, a tumor suppressor gene, involved in the apoptotic pathway through the formation of DISC complex in many tumors such as breast and gastric cancers [167,168]. In gastric cells, miR-21 upregulated and decreased PTEN expression, resulting in significant suppression of trastuzumab-induced apoptosis [168].…”