Differential expression profile of microRNAs in different types of uveal melanoma

Background

Researches showed that microRNA (miRNA) is involved in the pathogenesis and development of many tumors and plays a cancer-suppressing-gene like role or cancer-gene like action.Uveal melanoma (UM) is a common ocular malignant tumor in adult, and the mechanism of UM pathogenesis and metastasis is still not elucidated.Understanding the differential expression of miRNAs in UM is expected to provide a basis for targeting treatment of UM.

Objective

This study was to screen and compare the expression profiles of miRNAs in epithelial type and spindle type of UM.

Methods

The use of specimens of UM and donor eyes was approved by Ethic Commission of Capital Medical University.The specimens of epithelial type (4 specimens) and spindle type (4 specimens) of UM confirmed by histopathology and immunochemistry were collected in Beijing Tongren Hospital from March 2013 to October 2015.The expression profile of miRNA was assayed by miRNA array.Normal uveal specimens were obtained from 8 donors as controls.The differentially expressing miRNAs were screened by intergroup differential folds of ≥2.The genes targeting differentially expressed miRNAs were predicted using multiples online software and the potential signal pathway was further analyzed by bioinformatics method.The microarray outcomes were validated by real-time quantitative PCR.

Results

Spindle cell type and epithelial cell type of UMs were verified by hematoxylin and eosin staining.Immunochemistry showed that HMB45, melanin-A and S-100 were positively expressed in the two types of UM.Compared with the normal uveal tissue, 109 differentially expressed miRNAs, including 29 up-regulated and 80 down-regulated miRNAs were seen in the spindle cell type of UM, and in the epithelial cell type of UM, 50 differentially expressed miRNAs were found, including 23 up-regulated and 27 down-regulated miRNAs.In spindle cell type of UM, the up-regulated miRNAs were miR-146a-5p, miR-25-3p and miR-29b-1-5p, and down-regulated ones were miR-126-5p, miR-183-5p and miR-96-5p.In epithelial cell type of UM, the up-regulated miRNAs were miR-155-5p, miR-210 and miR-378a-5p, and down-regulated ones were miR-199a-5p, miR-143-3p and miR-143-5p.In addition, the mutual up-regulated miRNA in both spindle cell type of UM and epithelial cell type of UM were miR-132-3p, miR-21-5p, miR-34a-5p and miR-34b-5p, and mutual down-regulated ones were miR-125b-2-3p, miR-126-3p, miR-199a-3p and miR-214-3p.Bioinformatics analysis showed that the targeting genes predicted by differentially expressed miRNAs participated in a number of biological pathways, including cancer-related pathway, mitogen-activated protein kinase (MAPK) pathway, Wnt signal pathway and intercellular adhesion, endocytosis, prostatic cancer, colorectal cancer pathways.

Conclusions

Many differentially expressed miRNAs exist among spindle cell type of UM, epithelial cell type of UM and normal uveal tissue.These miRNAs participate in or regulate the biological behaviour of UM via different signal pathways.