Abstract
Dysregulated microRNA (miR)-625 expression has been observed in several kinds of cancer. MicroRNAs are important factors in the development and progression of malignant melanoma, though the clinical significance and function of miR-625 in human malignant melanoma remain unclear. Levels of miR-625 expression were therefore determined in 36 pairs of malignant melanoma and adjacent non-tumor tissue using qPCR. The effects of miR-625 dysregulation on malignant melanoma cell proliferation, wound healing, migration and invasion in vitro and tumorigenicity in vivo were investigated using CCK-8, transwell assays, and a nude mouse subcutaneous tumor model. Bioinformatics analysis and luciferase reporter system were used to predict and confirm the target gene of miR-625. miR-625 levels were frequently decreased in malignant melanoma. Ectopic expression of miR-625 suppressed proliferation, wound healing, migration, and tumorgenicity in malignant melanoma. Moreover, miR-625 acted, at least in part, by suppressing potential target SOX2. These results show that miR-625 is a tumor suppressor that inhibits the development and progression of malignant melanoma, which suggests miR-625 is potentially a new diagnostic marker and therapeutic target of malignant melanoma.
Highlights
Malignant melanoma, a skin cancer that arises from malignant transformation of melanocytes, is highly aggressive and metastatic [1]
Results suggested that reduction of miR-625 occurs in approximately 75% of human malignant melanoma (27/36 samples, Figure 1B), and the average relative expression level of miR-625 is significantly downregulated in tumor tissue compared with the non-tumor tissue (Figure 1C, *P < 0.05)
Because miR-625 is significantly downregulated in malignant melanoma, it might function as a tumor suppressor
Summary
A skin cancer that arises from malignant transformation of melanocytes, is highly aggressive and metastatic [1]. The malignant melanocytes show aberrant proliferation, resistance to apoptosis, and highly invasive potential and motility capacity, which are important biological characteristics in the aggressive clinical course of the metastatic disease [4, 5]. MicroRNAs (miRNAs) are noncoding small RNAs 18 to 22 nucleotides in length that regulate gene expression at the post-transcriptional level, and they influence many biological signaling pathways [7]. Many studies report significant deregulation of microRNAs expression profiling between tumor cells and cells derived from normal tissue, indicating that miRNAs function as either oncogenes or tumor suppressors in various cancers [9,10,11]
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