Shuting Liu1, Liang Chen2, Hua Chen1, Kangkang Xu1, Xi Peng1, Mingchang Zhang3. 1. Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, HB, China. 2. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, HB, China. 3. Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, HB, China. mingchangzhang@hotmail.com.
Abstract
BACKGROUND: The abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored. METHODS: The levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR) and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0119872 in the tumorigenesis of UM cells. The relationships among circ_0119872, miR-622 and G3BP1 were predicted using bioinformatic tools and verified by RNA-FISH, RNA pull-down and dual-luciferase reporter assays. The effects of circ_0119872 on Wnt/β-catenin and mTOR signalling pathways were determined by gene set enrichment analysis (GSEA) and western blotting. RESULTS: We found that circ_0119872 is upregulated in UM cell lines and tissues. Moreover, overexpression of circ_0119872 promotes the malignancy of UM cells, while silencing of circ_0119872 inhibits it. In addition, circ_0119872 can directly interact with miR-622 as a miRNA sponge that regulates the expression of the miR-622 target gene G3BP1 as well as downstream Wnt/β-catenin and mTOR signalling pathways. CONCLUSIONS: Circ_0119872 may act as an oncogene in UM through a novel circ_0119872/miR-622/G3BP1 axis, activating the Wnt/β-catenin and mTOR signalling pathways, which in turn may provide potential biomarkers and therapeutic targets for the management of UM.
BACKGROUND: The abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored. METHODS: The levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR) and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0119872 in the tumorigenesis of UM cells. The relationships among circ_0119872, miR-622 and G3BP1 were predicted using bioinformatic tools and verified by RNA-FISH, RNA pull-down and dual-luciferase reporter assays. The effects of circ_0119872 on Wnt/β-catenin and mTOR signalling pathways were determined by gene set enrichment analysis (GSEA) and western blotting. RESULTS: We found that circ_0119872 is upregulated in UM cell lines and tissues. Moreover, overexpression of circ_0119872 promotes the malignancy of UM cells, while silencing of circ_0119872 inhibits it. In addition, circ_0119872 can directly interact with miR-622 as a miRNA sponge that regulates the expression of the miR-622 target gene G3BP1 as well as downstream Wnt/β-catenin and mTOR signalling pathways. CONCLUSIONS: Circ_0119872 may act as an oncogene in UM through a novel circ_0119872/miR-622/G3BP1 axis, activating the Wnt/β-catenin and mTOR signalling pathways, which in turn may provide potential biomarkers and therapeutic targets for the management of UM.
Authors: Mariela Cortés-López; Matthew R Gruner; Daphne A Cooper; Hannah N Gruner; Alexandru-Ioan Voda; Alexander M van der Linden; Pedro Miura Journal: BMC Genomics Date: 2018-01-03 Impact factor: 3.969