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

Zhaoxia Xia, Chaoying Yang, Xiaoxi Yang, Shuduan Wu, Zhizhen Feng, Lei Qu, Xianghua Chen, Lingyu Liu, Yanling Ma

Department of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)

Med Sci Monit 2019; 25:8722-8732

DOI: 10.12659/MSM.917099

Available online:

Published: 2019-11-19


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.

Keywords: Cell Migration Assays, Cell Proliferation, Melanoma, MicroRNAs



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