Inhibition of HDAC2 sensitises antitumour therapy by promoting NLRP3/GSDMD-mediated pyroptosis in colorectal cancer

Xin Guan; Ruiqi Liu; Bojun Wang; Ruxin Xiong; Luying Cui; Yuanyu Liao; Yuli Ruan; Lin Fang; Xiaolin Lu; Xuefan Yu; Dan Su; Yue Ma; Tianjiao Dang; Zhuo Chen; Yuanfei Yao; Chao Liu; Yanqiao Zhang

doi:10.1002/ctm2.1692

Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (6) : e1692 DOI: 10.1002/ctm2.1692

RESEARCH ARTICLE

Inhibition of HDAC2 sensitises antitumour therapy by promoting NLRP3/GSDMD-mediated pyroptosis in colorectal cancer

Xin Guan ¹^,²^,³
, Ruiqi Liu ⁴
, Bojun Wang ¹^,²^,³
, Ruxin Xiong ¹^,²^,³
, Luying Cui ¹^,²^,³
, Yuanyu Liao ¹^,²^,³
, Yuli Ruan ¹^,²^,³
, Lin Fang ⁵
, Xiaolin Lu ⁶
, Xuefan Yu ¹^,²^,³
, Dan Su ¹^,²^,³
, Yue Ma ¹^,²^,³
, Tianjiao Dang ¹^,²^,³
, Zhuo Chen ¹^,²^,³
, Yuanfei Yao ¹^,²^,³^,^†
, Chao Liu ¹^,²^,³^,^†
, Yanqiao Zhang ¹^,²^,³^,^†

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Abstract

• Silencing of NLRP3 limits the GSDMD-dependent pyroptosis in colorectal cancer.

• HDAC2-mediated histone deacetylation leads to epigenetic silencing of NLRP3.

• HDAC2 suppresses the NLRP3 transcription by inhibiting the formation of H3K27ac/BRD4/p-P65 complex.

• Targeting HDAC2 activates pyroptosis and enhances therapeutic effect.

Keywords

colorectal cancer / H3K27ac / HDAC2 / NLRP3 / pyroptosis

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Xin Guan,Ruiqi Liu,Bojun Wang,Ruxin Xiong,Luying Cui,Yuanyu Liao,Yuli Ruan,Lin Fang,Xiaolin Lu,Xuefan Yu,Dan Su,Yue Ma,Tianjiao Dang,Zhuo Chen,Yuanfei Yao,Chao Liu,Yanqiao Zhang. Inhibition of HDAC2 sensitises antitumour therapy by promoting NLRP3/GSDMD-mediated pyroptosis in colorectal cancer. Clinical and Translational Medicine, 2024, 14(6): e1692 DOI:10.1002/ctm2.1692

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2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.