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. 2022 Jul 15;21:146. doi: 10.1186/s12943-022-01607-8

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 8 — CircPOLR2A enhanced the UBE3C-mediated ubiquitination of PEBP1. a After circPOLR2A knockdown or overexpression, western blotting detected the PEBP1 protein level in cRCC cells with UBE3C overexpression. Top, 786O cells with circPOLR2A knockdown; bottom, Caki1 cells with ectopic circPOLR2A expression. b, c Ubiquitination modification of PEBP1 in cRCC cells after ectopic UBE3C expression and circPOLR2A knockdown or overexpression detected via Co-IP and western blotting. 8b, 786O cells with circPOLR2A knockdown; 8c, Caki1 cells with ectopic circPOLR2A expression. d, e The binding of PEBP1 and UBE3C in cRCC cells after transfection with circPOLR2A knockdown (8d) or overexpression (8e) and treatment with 10 μg/ml RNase A. f, g Western blotting verified the activation of the ERK pathway in cRCC cells. 8f, 786O cells; 8 g, Caki1 cells. h Tube formation assay evaluated the angiogenesis of HUVECs incubated with the culture medium from cRCC cells transfected with circPOLR2A knockdown or overexpression. Top, 786O cells; bottom, Caki1 cells. Scale bar, 100 μm. i, j Tube formation assay for rescue experiments. 8i, 786O cells; 8j, Caki1 cells. Scale bar, 100 μm. k, l Statistical analysis on total number of junctions in the tube formation assay for rescue experiments