MicroRNA signatures differentiate melanoma subtypes

Chan, Eugenia L.; Patel, Rajeshvari; Nallur, Sunitha; Ratner, Elena; Bacchiocchi, Antonella; Hoyt, Kathleen; Szpakowski, Sebastian; Godshalk, Sirie E.; Ariyan, Stephan; Sznol, Mario; Halaban, Ruth; Krauthammer, Michael; Tuck, David; Slack, Frank J.; Weidhaas, Joanne B.

doi:10.4161/cc.10.11.15777

Cited by 86 publications

(72 citation statements)

References 36 publications

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“…Because p130Cas was downregulated by miR-362-3p and miR-329 without significant changes in the target mRNA levels, we assumed that miR-362-3p and miR-329 mediate translational repression of p130Cas and, accordingly, we examined de novo synthesis of p130Cas after miR overexpression. As expected, miR-362-3p and miR-329 decreased 35 S-labeled p130Cas in MCF7 cells, lending support to the notion of translational repression of p130Cas by miR-362-3p and miR-329 (Figure 1e).…”

supporting

confidence: 61%

“…Other studies have shown differential expression of miR-362-3p in various tissues including the fetal brain of mice, estrogen receptor-positive breast tumors, gastric cancer, and melanoma as well as downregulation of miR-329 in glioma, neuroblastoma, and the mouse model of Rett syndrome. 20,22,29,[33][34][35][36][37][38] The detailed mechanism, however, that governs the differential expression of the two miRs has not been fully elucidated.…”

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confidence: 99%

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Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Kang

et al. 2015

Cell Death Differ

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p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer. Cell Death and Differentiation (2016) 23, 484-495; doi:10.1038/cdd.2015; published online 4 September 2015 p130Cas/breast cancer anti-estrogen resistance 1 is a member of the Cas (Crk-associated substrate) family of adaptor proteins and has a central role in tyrosine kinasebased signaling related to cell adhesion, migration, cell cycle control, apoptosis, development, and cancer progression.

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supporting

confidence: 61%

mentioning

confidence: 99%

Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Kang

et al. 2015

Cell Death Differ

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“…Quantitative polymerase chain reaction (qPCR) of tumor samples revealed that let-7b, microRNA-199a, microRNA-33 and clinical transfer index (age, survival time, metastasis and death resulting from metastasis) are positively correlated (12). It has been reported that microRNA signatures differentiate melanoma subtypes; seven microRNAs (microRNA-142-3p, microRNA-486, m ic roR NA-214, m ic roR NA-218, m ic roR NA-362, microRNA-650 and microRNA-31) significantly correlated with acral melanoma compared to non-acral melanoma (15). Furthermore, let-7b and microRNA-199a were upregulated in uveal (ocular) melanoma, showing highly significant associations with the high metastatic gene expression signature and loss of chromosome 3, which have been shown to be more accurate predictors of metastasis than any clinical or pathological factors, and have served as surrogate endpoints for the identification of biomarkers in uveal melanoma (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

Let-7b and microRNA-199a inhibit the proliferation of B16F10 melanoma cells

Tan

Zhou

et al. 2012

Oncology Letters

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Abstract. Cutaneous melanoma is an aggressive form of human skin cancer characterized by high metastatic potential and poor prognosis. Biomarkers of metastatic risk are critically needed to instigate new auxiliary measures in high-risk patients. In clinical specimens of skin melanoma, we previously found that let-7b, microRNA-199a and microRNA-33 were significantly associated with metastatic melanoma, and thus may be the key to melanoma treatment. In this study, we examined the effect of overexpression and inhibition of let-7b and microRNA-199a. Plasmids overexpressing these genes were transfected into B16F10 melanoma cells, and let-7b and microRNA-199a expression were evaluated at the RNA, protein and cellular level. Cyclin D1 expression was significantly higher in cells transfected with let-7b plasmid and let-7b inhibitor compared with control cells (P<0.05). In turn, Met expression in the microRNA-199a plasmid group and microRNA-199a inhibitor group was significantly higher than in the control group (P<0.05). The proliferation rate of B16F10 cells transfected with let-7b or microRNA-199a was lower than that of the control group, particularly until the third day after transfection when the proliferation rate dropped to the lowest value (P<0.05). In addition, the apoptosis rates of the let-7b plasmid group and microRNA-199a plasmid group were significantly higher compared to that of the control group (P<0.05). These results suggest that let-7b and microRNA-199a may be negative regulators of B16F10 cell proliferation.

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“…8 In patients with cutaneous melanomas, Dicer upregulation was significantly associated with an increased tumor mitotic index, Breslow's depth of invasion, nodal metastasis, and a higher American Joint Committee on Caner (AJCC) clinical stage. 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.…”

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confidence: 99%

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

Babapoor

Kozubek

et al. 2017

Laboratory Investigation

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A comprehensive repertoire of human microRNAs (miRNAs) that could be involved in early melanoma invasion into the dermis remains unknown. To this end, we sequenced small RNAs (18-30 nucleotides) isolated from an annotated series of invasive melanomas (average invasive depth, 2.0 mm), common melanocytic nevi, and matched normal skin (n = 28). Our previously established bioinformatics pipeline identified 765 distinct mature known miRNAs and defined a set of top 40 list that clearly segregated melanomas into thin (0.75 mm) and thick (2.7 mm) groups. Among the top, miR-21-5p, let-7b-5p, let-7a-5p, miR-424-5p, miR-423-5p, miR-21-3p, miR-199b-5p, miR-182-5p, and miR-205-5p were differentially expressed between thin and thick melanomas. In a validation cohort (n = 167), measured expression of miR-21-5p and miR-424-5p, not previously reported in melanoma, were significantly increased in invasive compared with in situ melanomas (Po0.0001). Increased miR-21-5p levels were significantly associated with invasive depth (P = 0.038), tumor mitotic index (P = 0.038), lymphovascular invasion (P = 0.0036), and AJCC stage (P = 0.038). In contrast, let-7b levels were significantly decreased in invasive and in situ melanomas compared with common and dysplastic nevi (Po0.0001). Decreased let-7b levels were significantly associated with invasive depth (P = 0.011), Clark's level (P = 0.013), ulceration (P = 0.0043), and AJCC stage (P = 0.011). These results define a distinct set of miRNAs associated with invasive and aggressive melanoma phenotype. Notwithstanding the distinct sets of DNA and chromosomal alterations demonstrated in melanoma, the changes in the noncoding RNA transcriptome remain poorly understood. The microRNAs (miRNAs) are endogenous, noncoding small (18-24 nucleotides) RNAs, which can regulate gene expression in animals and plants by complementary base-pairing to the mRNAs of target genes to specify mRNA cleavage or translation repression. 1 Growing evidence has shown that particular miRNAs function predominately as tumor suppressors, eg, let-7 family 2,3 and miR-15a and miR-16; 4 and some as oncogenes, eg, miR-17~92 cluster. 5,6 A number of studies have demonstrated an evolving role of miRNAs in various aspects of melanoma biology and clinical behavior. For example, results showed a cell-specific upregulated Dicer expression in 81% of cutaneous, 80% of acrolentiginous, and 96% of metastatic melanomas compared with carcinomas or sarcomas of the skin. 7 Moreover, the expression of Dicer was significantly higher in melanomas compared with benign melanocytic nevi. Dicer, a member of the RNase III family of double-stranded RNases, is a central enzyme in a multi-component miRNA biogenesis pathway where the Drosha/DGCR8 complex and Dicer act sequentially to crop long primary and precursor miRNAs into functionally mature miRNAs. 8 In patients with cutaneous melanomas, Dicer upregulation was significantly associated with an increased tumor mitotic index, Breslow's depth of invasion, nodal metastasis, and a higher American Joi...

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MicroRNA signatures differentiate melanoma subtypes

Cited by 86 publications

References 36 publications

Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Let-7b and microRNA-199a inhibit the proliferation of B16F10 melanoma cells

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

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