气候变化领域集成服务门户(CCPortal): ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer

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DOI	10.1073/pnas.2015808118
	ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer
	Xiao Y.; Lin F.-T.; Lin W.-C.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Cisplatin is a mainstay of systemic therapy for a variety of cancers, such as lung cancer, head and neck cancer, and ovarian cancer. However, resistance to cisplatin represents one of the most significant barriers for patient outcome improvement. Actin-like 6A (ACTL6A) is a component of several chromatin remodeling complexes, including SWI/SNF, NuA4/TIP60 histone acetylase, and INO80. Amplification of ACTL6A gene is often seen in lung squamous cell carcinoma, ovarian cancer, and esophageal cancer, but its significance remains to be fully determined. Here we identify ACTL6A overexpression as a novel cause for platinum resistance. High levels of ACTL6A are associated with chemoresistance in several types of human cancer. We show that overexpression of ACTL6A leads to increased repair of cisplatin-DNA adducts and resistance to cisplatin treatment. In contrast, depletion of ACTL6A inhibits the repair of cisplatin-induced DNA lesions, and increases cisplatin sensitivity in cisplatin-resistant ovarian cancer cells. The regulation of repair by ACTL6A is mediated through the SWI/SNF chromatin remodeling complex. Treatment with a histone deacetylase inhibitor can reverse the effect of ACTL6A overexpression on the repair of cisplatin-induced DNA damage and render cancer cells more sensitive to cisplatin treatment in a xenograft mouse model. Taken together, our study uncovers a novel role for ACTL6A in platinum resistance, and provides evidence supporting the feasibility of using HDAC inhibitors for platinum resistant tumors. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ACTL6A; Cisplatin resistance; DNA repair; SWI/SNF
语种	英语
scopus关键词	actin like 6A; cisplatin; histone acetyltransferase; panobinostat; platinum; unclassified drug; ACTL6A gene; animal cell; animal experiment; animal model; Article; cancer cell; cancer resistance; chromatin assembly and disassembly; controlled study; depletion; DNA adduct; DNA damage; DNA repair; drug sensitivity; feasibility study; gene; gene expression level; gene identification; gene overexpression; in vivo study; lung cancer; malignant neoplasm; mouse; nonhuman; ovary cancer; priority journal
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180982
作者单位	Section of Hematology/Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, United States
推荐引用方式 GB/T 7714	Xiao Y.,Lin F.-T.,Lin W.-C.. ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer[J],2021,118(3).
APA	Xiao Y.,Lin F.-T.,&Lin W.-C..(2021).ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Xiao Y.,et al."ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).