Jiumei Zhao
1*
Yu Tang
3The final, formatted version of the article will be published soon.
REVIEW article
Front. Oncol.
Sec. Cancer Genetics
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1463892
This article is part of the Research Topic Exploring Epigenetic Mechanisms in Cancer View all 7 articles
Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors
Provisionally accepted- 1 Chongqing Nanchuan District People's Hospital, Nanchuan, China
- 2 Kunming Medical University, Kunming, Yunnan Province, China
- 3 Yunnan Cancer Hospital, Kunming, China
- 4 Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing, Chongqing Municipality, China
Abstracts: SWI/SNF (Switch/Sucrose non-fermentable, switch/sucrose non-fermentable) chromatin remodeling complex is a macromolecular complex composed of multiple subunits. It can use the energy generated by the hydrolysis of ATP (Adenosine triphosphate) to destroy the connection between DNA and histones, achieve the breakdown of nucleosomes, and regulate gene expression. SWI/SNF complex is essential for cell proliferation and differentiation, and the abnormal function of its subunits is closely related to tumorigenesis. Among them, ARID1A, an essential non-catalytic subunit of the SWI/SNF complex, can regulate the targeting of the complex through DNA or protein interactions. Moreover, the abnormal function of ARID1A significantly reduces the targeting of SWI/SNF complex to genes and participates in critical intracellular activities such as gene transcription and DNA synthesis. As a catalytic subunit of the SWI/SNF complex, SMARCA4 has ATPase activity that catalyzes the hydrolysis of ATP to produce energy and power the chromatin remodeling complex, which is critical to the function of the SWI/SNF complex. The study data indicate that approximately 25% of cancers have one or more SWI/SNF subunit genetic abnormalities, and at least nine different SWI/SNF subunits have been identified as having repeated mutations multiple times in various cancers, suggesting that mutations affecting SWI/SNF subunits may introduce vulnerabilities to these cancers. Here, we review the mechanism of action of ARID1A and SMARCA4, the two subunits with the highest mutation frequency in the SWI/SNF complex, and the research progress of their targeted therapy in tumors to provide a new direction for precise targeted therapy of clinical tumors.
Keywords: SWI/SNF complex, ARID1A, SMARCA4, tumor, Tumor resistance, molecular mechanism, targeted therapy
Received: 12 Jul 2024; Accepted: 15 Nov 2024.
Copyright: © 2024 Zhao, Zhu, Tang, Zheng and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jiumei Zhao, Chongqing Nanchuan District People's Hospital, Nanchuan, China
Jing Zhu, Kunming Medical University, Kunming, 650500, Yunnan Province, China
Kepu Zheng, Kunming Medical University, Kunming, 650500, Yunnan Province, China
Ziwei Li, Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing, 400065, Chongqing Municipality, China
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