Abstract

BACKGROUND: Dysregulation of the microRNA (miRNA) network is a typical feature of many cancers. However, the key specific miRNAs involved in uveal melanoma carcinogenesis are largely unknown.

MATERIAL AND METHODS: RT-qPCR was used to detected miR-652 expression in uveal melanoma tissues and cell lines. miR-652 inhibitor was transfected into uveal melanoma cells to decrease miR-652 expression and determine the biological role of miR-652 by CCK-8 and wound healing assays. Bioinformatic analysis and dual luciferase reporter assay were used to predict and validate the target gene of miR-652. HOXA9 siRNA was transfected into cells to confirm that miR-652 relies on regulation of HOXA9 to regulate cell proliferation and migration.

RESULTS: RT-qPCR showed that miR-652 was overexpressed in uveal melanoma cell lines (MUM-2B, MEL270) compared with melanocyte cells (ARPE-19). Overexpression of miR-652 was also observed in uveal melanoma compared to paired non-tumor tissues. Downregulation of miR-652 inhibited the cell proliferation ability and migration ability of uveal melanoma cells. Using bioinformatic analysis, HOXA9 was found to be a potential target gene of miR-652. The direct regulation of HOXA9 by miR-652 was experimentally validated in uveal melanoma cells by dual luciferase assay and Western blotting. We also observed that miR-652 promoted HIF-1α signaling via repression of HOXA9 in uveal melanoma cells. Silencing of HOXA9 attenuated the miR-652 inhibitor decreased cell growth rate and decreased migration ability in uveal melanoma cells.

CONCLUSIONS: Our data demonstrate an oncogenic role of miR-652 in uveal melanoma, showing that miR-652 may be a useful biomarker for prediction of prognosis for patients with uveal melanoma.

Keywords: Cell Migration Assays, Melanoma, Homeodomain Proteins, Uveal Neoplasms