Villora, Sarah Arroyo and Zhao, Yufen and Silva, Paula Castellanos and Hahn, Alba A. and Olanin, Vivien and Groll, David and Maurer, Sandra and Rötzer, Vera and Szymanski, Witold and Procida-Kowalski, Tara and Philipp, Niklas and Koch, Aline M. and Bartkuhn, Marek and Graumann, Johannes and Volckmann, Richard and Koster, Jan and Rossbach, Oliver and Salzig, Denise and Dammann, Reinhard and Sigges, Cornelia and Halbritter, Jan and Haerteis, Silke and Richter, Antje Maria (2025) Epigenetic silencing and CRISPR-mediated reactivation of tight junction protein claudin10b (CLDN10B) in renal cancer. CLINICAL EPIGENETICS, 17 (1): 102. ISSN 1868-7075, 1868-7083
Full text not available from this repository. (Request a copy)Abstract
BackgroundThe kidney's tubular system relies on cell polarity and tight junctions to maintain structure and function and disruptions contribute to diseases like cancer. Loss of tight junction proteins such as Claudins can actively contribute to tumorigenesis.ResultsWe aimed to identify biomarkers for renal carcinoma, after kidney transplantation and conventional kidney tumors. We identified the epigenetic silencing of the Claudin 10 gene isoform B (CLDN10B) through DNA hypermethylation in renal cancers, including clear cell (ccRCC), papillary (pRCC) and post-transplantation renal carcinoma (PT-ccRCC). In contrast, CLDN10A was hypomethylated in ccRCC and pRCC. Differential methylation of the isoforms discriminates RCC from other malignancies. The epigenetic alteration of CLDN10B significantly correlated with reduced patient survival and advanced tumor staging. CLDN10B overexpression or induction significantly inhibited migration, cell cycle progression, and cellular growth. Using a CRISPR-based epigenetic editing tool reactivated CLDN10B to its endogenous level using VP160 and TET1 by promoter demethylation and significantly demonstrated its tumor-suppressive effects in 2D and 3D cell models.ConclusionOur findings suggest that CLDN10B acts as a tumor suppressor, and its epigenetic regulation may represent a therapeutic target for RCC. Ultimately, understanding CLDN10B's regulation and function could provide new insights into renal cancer treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-SUPPRESSOR GENE; PROMOTER HYPERMETHYLATION; DNA METHYLATION; CELL; PLATFORM; INACTIVATION; STATISTICS; EXTRACTION; EXPRESSION; CARCINOMA; CLDN10; Renal cell carcinoma (RCC); DNA (hyper)methylation; Epigenetic editing; CRISPR-Cas9; Tumor suppressor |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Pflanzenwissenschaften > Lehrstuhl für Zellbiologie und Pflanzenphysiologie (Prof. Dr. Klaus Grasser) Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Jun 2026 11:53 |
| Last Modified: | 03 Jun 2026 11:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67365 |
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