miR-652 Promotes Proliferation and Migration of Uveal Melanoma Cells by Targeting HOXA9

Med Sci Monit. 2019 Nov 19:25:8722-8732. doi: 10.12659/MSM.917099.

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-1alpha 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.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Signal Transduction
  • Uveal Melanoma
  • Uveal Neoplasms / genetics*
  • Uveal Neoplasms / metabolism

Substances

  • Homeodomain Proteins
  • MIRN652 microRNA, human
  • MicroRNAs
  • homeobox protein HOXA9