PMID- 38347600
OWN - NLM
STAT- MEDLINE
DCOM- 20240220
LR  - 20240320
IS  - 1478-811X (Electronic)
IS  - 1478-811X (Linking)
VI  - 22
IP  - 1
DP  - 2024 Feb 12
TI  - Musashi-2 potentiates colorectal cancer immune infiltration by regulating the 
      post-translational modifications of HMGB1 to promote DCs maturation and 
      migration.
PG  - 117
LID - 10.1186/s12964-024-01495-z [doi]
LID - 117
AB  - Post-translational modifications (PTMs) of the non-histone protein high-mobility 
      group protein B1 (HMGB1) are involved in modulating inflammation and immune 
      responses. Recent studies have implicated that the RNA-binding protein (RBP) 
      Musashi-2 (MSI2) regulates multiple critical biological metabolic and 
      immunoregulatory functions. However, the precise role of MSI2 in regulating PTMs 
      and tumor immunity in colorectal cancer (CRC) remains unclear. Here, we present 
      data indicating that MSI2 potentiates CRC immunopathology in colitis-associated 
      colon cancer (CAC) mouse models, cell lines and clinical specimens, specifically 
      via HMGB1-mediated dendritic cell (DC) maturation and migration, further 
      contributes to the infiltration of CD4(+) and CD8(+) T cells and inflammatory 
      responses. Under stress conditions, MSI2 can exacerbate the production, 
      nucleocytoplasmic transport and extracellular release of damage-associated 
      molecular patterns (DAMPs)-HMGB1 in CRC cells. Mechanistically, MSI2 mainly 
      enhances the disulfide HMGB1 production and protein translation via direct 
      binding to nucleotides 1403-1409 in the HMGB1 3' UTR, and interacts with the 
      cytoplasmic acetyltransferase P300 to upregulate its expression, further 
      promoting the acetylation of K29 residue in HMGB1, thus leading to K29-HMGB1 
      nucleocytoplasmic translocation and extracellular release. Furthermore, blocking 
      HMGB1 activity with glycyrrhizic acid (Gly) attenuates MSI2-mediated 
      immunopathology and immune infiltration in CRC in vitro and in vivo. 
      Collectively, this study suggests that MSI2 may improve the prognosis of CRC 
      patients by reprogramming the tumor immune microenvironment (TIME) through 
      HMGB1-mediated PTMs, which might be a novel therapeutic option for CRC 
      immunotherapy.
CI  - (c) 2024. The Author(s).
FAU - Meng, Xiaole
AU  - Meng X
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Xiamen Clinical Research Center for Cancer Therapy; Department of Pathology, 
      Zhongshan Hospital (Xiamen Branch), Fudan University; National Institute for Data 
      Science in Health and Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Department of Pathology, Xiang'an Hospital of Xiamen University, School of 
      Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Organ Transplantation Clinical Medical Center of Xiamen University; Department of 
      General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, 
      Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Na, Risi
AU  - Na R
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Organ Transplantation Clinical Medical Center of Xiamen University; Department of 
      General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, 
      Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Peng, Xiao
AU  - Peng X
AD  - Organ Transplantation Clinical Medical Center of Xiamen University; Department of 
      General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, 
      Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Li, Hui
AU  - Li H
AD  - Department of Pathology, Xiang'an Hospital of Xiamen University, School of 
      Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Ouyang, Wanxin
AU  - Ouyang W
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Organ Transplantation Clinical Medical Center of Xiamen University; Department of 
      General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, 
      Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Zhou, Wenting
AU  - Zhou W
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Organ Transplantation Clinical Medical Center of Xiamen University; Department of 
      General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, 
      Xiamen University, Xiamen, Fujian, 361102, China.
FAU - You, Xuting
AU  - You X
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Department of Pathology, Xiang'an Hospital of Xiamen University, School of 
      Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Li, Yuhuan
AU  - Li Y
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Department of Pathology, Xiang'an Hospital of Xiamen University, School of 
      Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Pu, Xin
AU  - Pu X
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Department of Pathology, Xiang'an Hospital of Xiamen University, School of 
      Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Zhang, Ke
AU  - Zhang K
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
AD  - Department of Pathology, Xiang'an Hospital of Xiamen University, School of 
      Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Xia, Junjie
AU  - Xia J
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
FAU - Wang, Jie
AU  - Wang J
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. 
      wangjielj2012@163.com.
AD  - Organ Transplantation Clinical Medical Center of Xiamen University; Department of 
      General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, 
      Xiamen University, Xiamen, Fujian, 361102, China. wangjielj2012@163.com.
FAU - Tang, Huamei
AU  - Tang H
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. 
      tanghuamei2014@163.com.
AD  - Department of Pathology, Xiang'an Hospital of Xiamen University, School of 
      Medicine, Xiamen University, Xiamen, Fujian, 361102, China. 
      tanghuamei2014@163.com.
FAU - Zhuang, Guohong
AU  - Zhuang G
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. 
      zhgh@xmu.edu.cn.
FAU - Peng, Zhihai
AU  - Peng Z
AD  - Organ Transplantation Institute of Xiamen University; Xiamen Human Organ 
      Transplantation Quality Control Center; Xiamen Key Laboratory of Regeneration 
      Medicine; Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, 
      School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. 
      pengzhihai1958@163.com.
AD  - Organ Transplantation Clinical Medical Center of Xiamen University; Department of 
      General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, 
      Xiamen University, Xiamen, Fujian, 361102, China. pengzhihai1958@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240212
PL  - England
TA  - Cell Commun Signal
JT  - Cell communication and signaling : CCS
JID - 101170464
RN  - 0 (HMGB1 Protein)
RN  - 0 (MSI2 protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (HMGB1 protein, human)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - CD8-Positive T-Lymphocytes
MH  - *Colorectal Neoplasms/metabolism
MH  - Cytosol/metabolism
MH  - *HMGB1 Protein/metabolism
MH  - Protein Processing, Post-Translational
MH  - RNA-Binding Proteins/genetics
MH  - Tumor Microenvironment
PMC - PMC10863188
OTO - NOTNLM
OT  - Colorectal cancer (CRC)
OT  - HMGB1
OT  - Immune infiltration
OT  - Musashi-2
OT  - Post-translational modifications (PTMs)
COIS- The authors declare no competing interest.
EDAT- 2024/02/13 00:42
MHDA- 2024/02/13 06:46
PMCR- 2024/02/12
CRDT- 2024/02/12 23:47
PHST- 2023/11/16 00:00 [received]
PHST- 2024/01/21 00:00 [accepted]
PHST- 2024/02/13 06:46 [medline]
PHST- 2024/02/13 00:42 [pubmed]
PHST- 2024/02/12 23:47 [entrez]
PHST- 2024/02/12 00:00 [pmc-release]
AID - 10.1186/s12964-024-01495-z [pii]
AID - 1495 [pii]
AID - 10.1186/s12964-024-01495-z [doi]
PST - epublish
SO  - Cell Commun Signal. 2024 Feb 12;22(1):117. doi: 10.1186/s12964-024-01495-z.