HMGB1 mediates lipopolysaccharide-induced inflammation via interacting with GPX4 in colon cancer cells

Cancer Cell International
Yuhan YangKejian Pan

Abstract

Inflammation is one of a main reason for colon cancer progression and poor prognosis. The high-mobility group box-1 (HMGB1) and glutathione peroxidase 4 (GPX4) are responsible for inflammation, but the relationship between HMGB1 and GPX4 remains unknown about inflammation in colon cancer. RT-qPCR was carried out to investigate the expression of IL1β, IL6 and TNFα in colon cancer cells stimulated with LPS or siHMGB1. To observe the relationship between HMGB1, GPX4 and inflammation or ROS, Western blot assays were adopted. Pull-down, CoIP and immunohistochemistry assays were performed to further investigate the molecular mechanisms of HMGB1 and GPX4 in colon cancer. We report that HMGB1 mediates lipopolysaccharide (LPS)-induced inflammation in colon cancer cells. Mechanistically, acetylated HMGB1 interacts with GPX4, negatively regulating GPX4 activity. Furthermore, by utilizing siHMGB1 and its inhibitor, our discoveries demonstrate that HMGB1 knockdown can inhibit inflammation and reactive oxygen species (ROS) accumulation via NF-kB. Collectively, our findings first demonstrate that acetylated HMGB1 can interact with GPX4, leading to inflammation, and providing therapeutic strategies targeting HMGB1 and GPX4 for colon cancer.

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Citations

Aug 25, 2020·Journal of Hematology & Oncology·Shumin Wang, Yi Zhang
Feb 14, 2021·Journal of Orthopaedic Surgery and Research·Chao LiTian Lan
Nov 26, 2021·Expert Opinion on Therapeutic Targets·Long YeYun Dai
Jan 16, 2022·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Youchao QiNing Peng

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Methods Mentioned

BETA
acetylation
PCR
transfection
Assay
MDA
Pulldown
immunoprecipitation

Software Mentioned

GraphPad Prism
SPSS

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