Pavičić, I.; Rokić, F.; Vugrek, O. Effects of S-Adenosylhomocysteine Hydrolase Downregulation on Wnt Signaling Pathway in SW480 Cells. Int. J. Mol. Sci.2023, 24, 16102.
Pavičić, I.; Rokić, F.; Vugrek, O. Effects of S-Adenosylhomocysteine Hydrolase Downregulation on Wnt Signaling Pathway in SW480 Cells. Int. J. Mol. Sci. 2023, 24, 16102.
Pavičić, I.; Rokić, F.; Vugrek, O. Effects of S-Adenosylhomocysteine Hydrolase Downregulation on Wnt Signaling Pathway in SW480 Cells. Int. J. Mol. Sci.2023, 24, 16102.
Pavičić, I.; Rokić, F.; Vugrek, O. Effects of S-Adenosylhomocysteine Hydrolase Downregulation on Wnt Signaling Pathway in SW480 Cells. Int. J. Mol. Sci. 2023, 24, 16102.
Abstract
Disorder of S-adenosylhomocysteine hydrolase (AHCY) activity leads to the potentially lethal rare disease AHCY deficiency, first described in 2004 by Baric and co-workers [1]. In order to shed new light on molecular aspects of the disease, in particular changes at transcriptome level, we enabled knock-down of AHCY expression in model systems such as the colon cancer cell line SW480 to simulate the environment occurring in AHCY deficiency patients. Further, we per-formed deep sequencing of mRNA, followed by differential expression and molecular pathway analysis. Fifteen differentially expressed networks were identified, and interestingly, we found a predicted effect of AHCY down-regulation on the expression of the Lymphoidphoid enhanc-er-binding factor 1 (LEF1) gene, indicating changes in the TCF4/LEF1 complex. LEF1, a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a down-stream mediator of the Wnt/β-catenin signaling pathway [2]. LEF1 is essential in stem cell maintenance, and especially in its role in epithelial-mesenchymal transition (EMT). Western blot analysis of LEF1 protein expression confirmed our transcriptomic data predictions and revealed significantly increased LEF1 protein in AHCY- deficient cells, providing a novel link between AHCY and cancer cell phenotype.
Biology and Life Sciences, Biochemistry and Molecular Biology
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