e-Article
Depletion of NK6 Homeobox 3 (NKX6.3) causes gastric carcinogenesis through copy number alterations by inducing impairment of DNA replication and repair regulation.
Document Type
Academic Journal
Author
Yoon JH; Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea.; Eun JW; Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.; Ashktorab H; Department of Medicine, Howard University, Washington, DC, USA.; Smoot DT; Department of Medicine, Meharry Medical Center, Nashville, TN, USA.; Kim JK; Department of Life Science, Chung-Ang University, Seoul, South Korea.; Nam SW; Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea.; Park WS; Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea. wonsang@catholic.ac.kr.
Source
Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101580004 Publication Model: Electronic Cited Medium: Print ISSN: 2157-9024 (Print) Linking ISSN: 21579024 NLM ISO Abbreviation: Oncogenesis Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2157-9024
Abstract
Genomic stability maintenance requires correct DNA replication, chromosome segregation, and DNA repair, while defects of these processes result in tumor development or cell death. Although abnormalities in DNA replication and repair regulation are proposed as underlying causes for genomic instability, the detailed mechanism remains unclear. Here, we investigated whether NKX6.3 plays a role in the maintenance of genomic stability in gastric epithelial cells. NKX6.3 functioned as a transcription factor for CDT1 and RPA1, and its depletion increased replication fork rate, and fork asymmetry. Notably, we showed that abnormal DNA replication by the depletion of NKX6.3 caused DNA damage and induced homologous recombination inhibition. Depletion of NKX6.3 also caused copy number alterations of various genes in the vast chromosomal region. Hence, our findings underscore NKX6.3 might be a crucial factor of DNA replication and repair regulation from genomic instability in gastric epithelial cells.
(© 2021. The Author(s).)
(© 2021. The Author(s).)