Vanguard is a Glucose Deprivation‐Responsive Long Non‐Coding RNA Essential for Chromatin Remodeling‐Reliant DNA Repair
Source abstract
Abstract
Abstract Glucose metabolism contributes to DNA damage response pathways by regulating chromatin remodeling, double‐strand break (DSB) repair, and redox homeostasis, although the underlying mechanisms are not fully established. Here, a previously uncharacterized long non‐coding RNA is revealed that is call Vanguard which acts to promote HMGB1‐dependent DNA repair in association with changes in global chromatin accessibility. Vanguard expression is maintained in cancer cells by SP1‐dependent transcription according to glucose availability and cellular adenosine triphosphate (ATP) levels. Vanguard promotes complex formation between HMGB1 and HDAC1, with the resulting deacetylation of HMGB1 serving to maintain its nuclear localization and DSB repair function. However, Vanguard downregulation under glucose limiting conditions promotes HMGB1 translocation from the nucleus, increasing DNA damage, and compromising cancer cell growth and viability. Moreover, Vanguard silencing increases the effectiveness of poly (ADP‐ribose) polymerase inhibitors against breast cancer cells with wild‐type breast cancer gene‐1 status, suggesting Vanguard as a potential therapeutic target.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Cancer-related molecular mechanisms research · RNA modifications and cancer · NF-κB Signaling Pathways
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Hepatobiliary Surgery The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui 230001 China
Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer People's Hospital of Zhengzhou University Academy of Medical Sciences Zhengzhou University Zhengzhou Henan 450053 China
The Cancer Hospital of the University of Chinese Academy of Sciences Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Hangzhou Zhejiang 310022 China
Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery The First Affiliated Hospital of USTC Hefei Anhui 230001 China
Anhui Provincial Clinical Research Center for Hepatobiliary Diseases The First Affiliated Hospital of USTC Hefei Anhui 230001 China
Funding
National Natural Science Foundation of China · China Postdoctoral Science Foundation
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