MicroRNA Expression Profile in Conjunctival Melanoma

Abstract

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...

Micro RNA Transcriptome Profile in Canine Oral Melanoma

“…Moreover, we detected several differentially expressed miRNAs that have not been reported previously (Table S2). [22][23][24][25][26]. The expression trends of these miRNAs correlated well between human melanoma and COM.…”

Differential miRNA Expression in Basaloid Squamous Cell Carcinoma of the Oesophagus: miR-3687 Targets PGRMC2

“…A literature search on miR-3687 retrieved only a few articles related to malignant neoplasia. One study has referred to invasive ability and poor prognosis of oesophageal cancer, another to increasing local recurrence of conjunctival melanoma and a third to telomerase activity of a breast cancer cell line (30,33,34). The present study was the first to investigate both miR-3687 as a differentially expressed miRNA in BSCCE and its putative target genes in oesophageal carcinoma.…”

High miR-3687 Expression Affects Migratory and Invasive Ability of Oesophageal Carcinoma

“…Therefore, cases with high expression of miR-3687 resemble BSCCE with aggressive biological features, resulting in poor prognosis. It was reported that miR-3687 was highly expressed in conjunctival melanoma; moreover, miR-3687 upregulation was also related to high risk of local recurrence (33). However, no study to date has assessed the impact of miR-3687 in oesophageal cancer.…”