1. RNA binding protein ZCCHC24 promotes tumorigenicity in triple-negative breast cancer.
- Author
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Uchida Y, Kurimoto R, Chiba T, Matsushima T, Oda G, Onishi I, Takeuchi Y, Gotoh N, and Asahara H
- Subjects
- Humans, Female, Animals, Cell Line, Tumor, Mice, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Zinc Finger E-box-Binding Homeobox 1 metabolism, Zinc Finger E-box-Binding Homeobox 1 genetics, Carcinogenesis genetics, Triazoles pharmacology, Cell Proliferation, Gene Knockdown Techniques, Xenograft Model Antitumor Assays, Azepines, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms metabolism, Triple Negative Breast Neoplasms pathology, RNA-Binding Proteins metabolism, RNA-Binding Proteins genetics, Gene Expression Regulation, Neoplastic
- Abstract
Triple-negative breast cancer (TNBC) lacks the expression of hormone and HER2 receptors and is highly malignant with no effective therapeutic targets. In TNBC, the cancer stem-like cell (CSC) population is considered to be the main cause of resistance to treatment. Thus, the therapeutic targeting of this population could substantially improve patient survival. Here, we identify the RNA-binding protein ZCCHC24 as enriched in the mesenchymal-like TNBC population. ZCCHC24 promotes the expression of a set of genes related to tumorigenicity and treatment resistance by directly binding to the cis-element "UGUWHWWA" in their mRNAs, thereby stabilizing them. One of the ZCCHC24 targets, ZEB1, is a transcription factor that promotes the expression of cancer stemness genes and reciprocally induces ZCCHC24 expression. ZCCHC24 knockdown by siRNAs shows a therapeutic effect and reduces the mesenchymal-like cell population in TNBC patient-derived xenografts. ZCCHC24 knockdown also has additive effects with the BET inhibitor JQ1 in suppressing tumor growth in TNBC patient-derived xenografts., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2024. The Author(s).)
- Published
- 2024
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