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Compound AC1Q3QWB upregulates CDKN1A and SOX17 by interrupting the HOTAIR-EZH2 interaction and enhances the efficacy of tazemetostat in endometrial cancer.
- Source :
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Cancer letters [Cancer Lett] 2023 Dec 01; Vol. 578, pp. 216445. Date of Electronic Publication: 2023 Oct 20. - Publication Year :
- 2023
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Abstract
- Endometrial cancer (EC) is a common malignancy of the female reproductive system, with an escalating incidence. Recurrent/metastatic EC presents a poor prognosis. The interaction between the long non-coding RNA (lncRNA) HOTAIR and the polycomb repressive complex 2 (PRC2) induces abnormal silencing of tumor suppressor genes, exerting a pivotal role in tumorigenesis. We have previously discovered AC1Q3QWB (AQB), a small-molecule compound targeting HOTAIR-EZH2 interaction. In the present study, we unveil that AQB selectively hampers the interaction between HOTAIR and EZH2 within EC cells, thus reversing the epigenetic suppression of tumor suppressor genes. Furthermore, our findings demonstrate AQB's synergistic effect with tazemetostat (TAZ), an EZH2 inhibitor, significantly boosting the expression of CDKN1A and SOX17. This, in turn, induces cell cycle arrest and impedes EC cell proliferation, migration, and invasion. In vivo experiments further validate AQB's potential by enhancing TAZ's anti-tumor efficacy at lower doses. Our results advocate AQB, a recently discovered small-molecule inhibitor, as a promising agent against EC cells. When combined with TAZ, it offers a novel therapeutic strategy for EC treatment.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Female
Enhancer of Zeste Homolog 2 Protein genetics
Enhancer of Zeste Homolog 2 Protein metabolism
Neoplasm Recurrence, Local genetics
Gene Expression Regulation, Neoplastic
Cell Line, Tumor
SOXF Transcription Factors genetics
SOXF Transcription Factors metabolism
Cyclin-Dependent Kinase Inhibitor p21 genetics
Endometrial Neoplasms drug therapy
Endometrial Neoplasms genetics
RNA, Long Noncoding genetics
RNA, Long Noncoding metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 578
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 37866545
- Full Text :
- https://doi.org/10.1016/j.canlet.2023.216445