Signatures of MicroRNAs and Selected MicroRNA Target Genes in Human Melanoma

Abstract

Small noncoding microRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation or orchestrating their sequence-specific degradation. In this study, we investigated miRNA and miRNA target gene expression patterns in melanoma to identify candidate biomarkers for early and progressive disease. Because data presently available on miRNA expression in melanoma are inconsistent thus far, we applied several different miRNA detection and profiling techniques on a panel of 10 cell lines and 20 patient samples representing nevi and primary or metastatic melanoma. Expression of selected miRNAs was inconsistent when comparing cell line-derived and patient-derived data. Moreover, as expected, some discrepancies were also detected when miRNA microarray data were correlated with qPCR-measured expression levels. Nevertheless, we identified miRNA-200c to be consistently downregulated in melanocytes, melanoma cell lines, and patient samples, whereas miRNA-205 and miRNA-23b were markedly reduced only in patient samples. In contrast, miR-146a and miR-155 were upregulated in all analyzed patients but none of the cell lines. Whole-genome microarrays were performed for analysis of selected melanoma cell lines to identify potential transcriptionally regulated miRNA target genes. Using Ingenuity pathway analysis, we identified a deregulated gene network centered around microphthalmia-associated transcription factor, a transcription factor known to play a key role in melanoma development. Our findings define miRNAs and miRNA target genes that offer candidate biomarkers in human melanoma. Cancer Res; 70(10); 4163-73. ©2010 AACR.

MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer

“…MiR-205 expression level is reportedly upregulated in human samples of lung cancer, 69 bladder cancer, 70 and endometrioid adenocarcinoma, 71 and downregulated in breast cancer, [72][73][74] prostate cancer, 75 and melanoma. 76 It has been reported that in a cohort of early breast cancer patients, decreased miR-205 is associated with worse disease-free interval and overall survival. 77 Similarly, in our cohort of advanced breast cancer patients, lower miR-205 expression is also associated with worse survival.…”

MicroRNA-146a Inhibits Glioma Development by Targeting Notch1

“…These miRNAs are rarely expressed in gliomas; however, their overexpression restrains proliferation and self-renewal of glioma stem-like cells by promoting neural differentiation (20,21). miR-146a is unique in that it is significantly enriched in the human tissues of skin (melanoma), cervical, breast, pancreas and prostate cancers compared to the same noncancerous tissues (42,51,53). Similarly, miR-146a was also upregulated in human glioblastoma tissues and in both human and mouse primary glioma cell lines (32).…”

Identification of microRNAs associated with invasive and aggressive phenotype in cutaneous melanoma by next-generation sequencing

“…7 Based on microarray hybridization or real-time quantitative RT-PCR (qRT-PCR), results show specific miRNAs being deregulated in some melanoma cell lines, 9,[10][11][12][13] in melanoma metastases, 14 and in primary melanomas. [15][16][17] Moreover, an expression signature, consisting of 18 miRNAs identified in metastatic specimens, significantly correlated with longer survival in a cohort of melanoma patients. 14 Next-generation sequencing of small RNAs isolated from common melanocytic nevi, thick primary melanomas (44.0 mm in invasive depth) and metastatic melanomas to skin and lymph nodes revealed a top 40 list of key miRNAs that correctly distinguished benign from malignant melanocytic tumors.…”

“…7 Based on microarray hybridization or real-time quantitative RT-PCR (qRT-PCR), results show specific miRNAs being deregulated in some melanoma cell lines, 9,10-13 in melanoma metastases, 14 and in primary melanomas. [15][16][17] Moreover, an expression signature, consisting of 18 miRNAs identified in metastatic specimens, …”