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. 2024 Dec 21;14:153. doi: 10.1186/s13578-024-01333-2

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© The Author(s) 2024

Open Access This 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. 6 — UHRF1 inhibitor (NSC232003) specifically inhibits SIRT6-deficient BLCA. A Dose–response curves and IC50 in a panel of BLCA cells treated with NSC232003. Data are presented as mean + / − SD (n = 6) from one-of-three independent experiments. B CCK-8 analysis showed the cell viability of indicated cells treated with increasing doses of NSC232003. C Colony formation assays showed the sensitivity of indicated cells to increasing doses of NSC232003. D-E Mouse weight changes measurements D (n = 5) and complete blood counts E assessed on vehicle control and NSC232003-treated mice. F Representative immunohistochemical staining against SIRT6 in PDXs derived from SIRT6-low and -high BLCA specimens. G Tumor volumes of indicated PDXs treated with NSC232003 (n = 6). H Illustration of SIRT6-UHRF1-MCT4 axis in regulating BLCA lactate secretion and progression. *p < 0.05, **p < 0.01, ***p < 0.001, ns no significance