miR-146a Exerts Differential Effects on Melanoma Growth and Metastatization

Raimo, M.; Orso, F.; Grassi, E.; Cimino, D.; Penna, E.; Pitta, C. De; Stadler, M. B.; Primo, L.; Calautti, E.; Quaglino, P.; Provero, P.; Taverna, D.

doi:10.1158/1541-7786.mcr-15-0425

Cited by 5 publications

(7 citation statements)

References 22 publications

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“…In the present study, we performed an expression analysis of 2578 mature human miRNAs and identified 24 significantly upregulated miRNAs and 1 significantly downregulated miRNA in CM versus normal conjunctiva. Whereas several of these miRNAs have previously been described in cutaneous melanoma, 15,16,18,[21][22][23][24][25][26][27][28][29][30][31] none have been reported previously in UM samples. 17,32,33 It was not possible to collect paired normal tissue for the comparison with CM, which may have limited the number of significant miRNAs identified in the present study.…”

Section: Discussionmentioning

confidence: 88%

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MicroRNA Expression Profile in Conjunctival Melanoma

Larsen

Mikkelsen

Borup

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Conjunctival melanoma (CM) is a rare disease associated with considerable mortality. As opposed to cutaneous melanoma, the epigenetic mechanisms involved in the development of CM and other mucosal melanomas (MMs) are unclear. The purpose of this study was to identify tumor-specific and prognostic microRNA (miRNA) in CM and to compare the miRNA profile with that of MM.METHODS. Using microarray analysis (Affymetrix) we determined the miRNA expression profile in 40 CMs compared with 7 normal conjunctival samples. Changes in miRNA expression were associated with T stage, local recurrence, metastasis, and mortality. Furthermore, the expression of six fresh frozen tissue samples of CM was compared with that of four laryngeal and sinonasal MM.RESULTS. Our analysis revealed 24 upregulated and 1 downregulated miRNA in CM; several of these miRNAs have key functions in the pathogenesis and progression of cutaneous melanoma. Additionally, we identified seven upregulated miRNAs specific for stage-T1 and stage-T2 CM, whose expression was associated with increased tumor thickness (P ¼ 0.007), and two upregulated miRNAs (miR-3687 and miR-3916) associated with an increased risk of local recurrence. No stage T3-specific miRNAs were identified.CONCLUSIONS. We identified differentially expressed and potentially prognostic miRNAs in CM. Furthermore, the miRNA expression pattern of CM resembled that in MM. The identification of these differentially expressed miRNAs provides an entry point for future functional studies of miRNAs as prognostic or therapeutic targets in CM and highlights the resemblance between CM, MM, and cutaneous melanoma.Keywords: conjunctiva, melanoma, microRNA, gene expression C onjunctival melanomas (CMs) account for approximately 5% of ocular melanomas and they have an associated mortality of up to 30%. 1,2 Recently, oncogenic mutations in BRAF, NRAS, and KIT have been identified in CM, emphasizing their close genetic resemblance to cutaneous and mucosal melanomas (MMs), and their difference from uveal melanomas (UMs). [2][3][4][5] Owing to the high mortality rate associated with CM and MM, 2,6 there is a need to further identify molecular pathways that drive development and progression. MicroRNAs (miRNAs) are small noncoding RNA molecules that epigenetically regulate gene expression at the posttranscriptional level by either degradation of or translational blockage of target messenger RNAs.7 Deregulation of miRNAs with oncogenic and tumor-suppressive functions have attracted much attention owing to their high prevalence.8 These small miRNA molecules could be used as prognostic or therapeutic targets. A microarray-based miRNA expression profiling platform was therefore used to compare the expression of miRNAs in archived (formalin-fixed, paraffin-embedded [FFPE]) CM and normal conjunctival samples. The miRNA expression pattern in CM was tested for associations with TNM stage, 9 local recurrence, metastasis, and mortality in order to identify prognostic miRNAs. To determine similarities in miRNA expressi...

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Section: Discussionmentioning

confidence: 88%

“…Upregulation of miR-146a has been observed in primary and metastatic cutaneous melanoma, and it may be specific for metastatic disease. 26,29,31 miR-146a promotes both initiation and progression of BRAF/NRAS-mutated cutaneous melanoma through increased activation of the NOTCH protein.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Profile in Conjunctival Melanoma

Larsen

Mikkelsen

Borup

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…The selected primer/probe assays (Life Technologies) included cel-miR-39-3p (assay ID000200), hsa-miR-425-5p (assay ID001516), mmu-miR-134 (assay ID001186), hsa-miR-145 (assay ID002278), hsa-miR-146a (assay ID000468), hsa-miR-365 (assay ID001020) and hsa-miR-223-3p (assay ID002295). 30,39,2,22,51,36,26,35 Quantitative reactions were performed in duplicate in scaled-down (12 l) reaction volumes using 6 l TaqMan 2X Universal Master Mix II (Applied Biosystems, catalog number 4440044), 0.6 l miRNA specific TaqMan Assay 20X and 1l of the RT product per reaction on Eco Real Time PCR detection System (Illumina). The standard cycling program was 50°C for 2 min, 95°C for 10 min and 40 cycles of 95°C for 15 sec and 60°C for 60 sec.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…To the best of authors' knowledge, few data are available on the expression patterns of miRNA in oral and cutaneous canine malignant melanoma when compared to healthy controls. The aims of the present study were 1) to screen by RT-qPCR the expression of a panel of miRNAs, previously demonstrated to be related to melanoma (miR-425-5p, miR-134, miR-145, miR-146a, miR-223-3p and miR-365), 30,39,2,22,51,36,26,35 in a cohort of oral and cutaneous malignant melanoma; 2) to carry out functional enrichment analysis of target genes and functional interaction network analysis, to identify pathways affected by the differentially expressed miRNAs.…”

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confidence: 99%

MicroRNA Expression in Formalin-Fixed, Paraffin-Embedded Samples of Canine Cutaneous and Oral Melanoma by RT-qPCR

et al. 2019

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MicroRNAs (miRNAs) are a class of small, noncoding RNA that post-transcriptionally regulate protein expression. miRNAs are emerging as clinical biomarkers of many diseases, including tumors. The aim of this study was to investigate whether miRNA expression could vary in melanoma samples derived from formalin-fixed, paraffin-embedded (FFPE) tissues. The study included 4 groups: (1) 9 samples of oral canine malignant melanoma, (2) 10 samples of cutaneous malignant melanoma, (3) 5 samples of healthy oral mucosa, and (4) 7 samples of healthy skin. The expression levels of 6 miRNAs—miR-145, miR-146a, miR-425-5p, miR-223, miR-365, and miR-134—were detected and assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) using TaqMan probes. Cutaneous canine malignant melanoma showed a decrease of the expression level of miR-145 and miR-365 and an increase of miR-146a and miR-425-5p compared to control samples. MiR-145 was also downregulated in oral canine malignant melanoma. The miRNAs with decreased expression may regulate genes involved in RAS, Rap1, and transforming growth factor β (TGF-β) signaling pathways, as well as upregulated genes associated with phosphatidylinositol signaling system, adherens junction, and RAS signaling pathways. In conclusion, miR-145, miR-365, miR-146a, and miR-425-5p were differentially expressed in canine malignant melanoma and healthy FFPE samples, suggesting that they may play a role in canine malignant melanoma pathogenesis.

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“…Likewise, RMEL3 has been described as an enriched lncRNA in melanoma tumors [21,28], while BANCR stimulates MAPK pathways and the NOTCH cascade by sequestering miR-204 so that it is no longer able to repress NOTCH2 [22]. Meanwhile, miR-146a also participates in the regulation of this cascade by targeting LFNG (LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) and the protein encoded by NUMB (numb homolog) [29,30]. Finally, tumor cell proliferation is also enhanced in melanoma cells by the lncRNA SAMMSON (survival associated mitochondrial melanoma-specific oncogenic noncoding RNA) that confers a growth advantage to melanoma cells.…”

Section: Non-coding Rnas Maintain Proliferative Signaling In Melanomamentioning

confidence: 99%

Non-Coding RNAs in Cutaneous Melanoma Development, Progression and Dissemination

Vignard¹,

Fradin²

2018

obm.genet.

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Melanoma is a highly aggressive skin cancer with high incidence worldwide. There is growing evidence that aberrantly expressed non-coding RNAs (ncRNAs) play a role in the development, progression and dissemination of melanoma tumor cells. Among the many types of ncRNAs described in this review, the functions of micro-and long non-coding RNAs are described and related to the six hallmarks of cancer. Recently, ncRNAs discovered in body fluids have become known as one of the most promising groups of oncological biomarkers for use in non-invasive diagnosis, prognosis or therapeutic response prediction.

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miR-146a Exerts Differential Effects on Melanoma Growth and Metastatization

Cited by 5 publications

References 22 publications

MicroRNA Expression Profile in Conjunctival Melanoma

MicroRNA Expression Profile in Conjunctival Melanoma

MicroRNA Expression in Formalin-Fixed, Paraffin-Embedded Samples of Canine Cutaneous and Oral Melanoma by RT-qPCR

Non-Coding RNAs in Cutaneous Melanoma Development, Progression and Dissemination

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