PMID- 36064319
OWN - NLM
STAT- MEDLINE
DCOM- 20220907
LR  - 20220914
IS  - 1689-1392 (Electronic)
IS  - 1425-8153 (Print)
IS  - 1425-8153 (Linking)
VI  - 27
IP  - 1
DP  - 2022 Sep 5
TI  - Pou3f1 mediates the effect of Nfatc3 on ulcerative colitis-associated colorectal 
      cancer by regulating inflammation.
PG  - 75
LID - 10.1186/s11658-022-00374-0 [doi]
LID - 75
AB  - BACKGROUND: Ulcerative colitis-associated colorectal cancer (UC-CRC) is an 
      important complication of ulcerative colitis. Pou3f1 (POU class 3 homeobox 1) is 
      a critical regulator for developmental events and cellular biological processes. 
      However, the role of Pou3f1 in the development of UC-CRC is unclear. METHODS: In 
      vivo, a UC-CRC mouse model was induced by azoxymethane (AOM) and dextran sulfate 
      sodium (DSS). Body weight, colon length, mucosal damage, tumor formation, and 
      survival rate were assessed to determine the progression of UC-CRC. Western blot, 
      quantitative real-time PCR, ELISA, immunohistochemistry, immunofluorescence and 
      TUNEL were performed to examine the severity of inflammation and tumorigenesis. 
      In vitro, LPS-treated mouse bone marrow-derived macrophages (BMDMs) and RAW264.7 
      cells were used to study the role of Pou3f1 in inflammation. ChIP and luciferase 
      reporter assays were used to confirm the interaction between Nfatc3 and Pou3f1. 
      RESULTS: Pou3f1 expression was increased in the colons of UC-CRC mice, and its 
      inhibition attenuated mucosal injury, reduced colon tumorigenesis and increased 
      survival ratio. Knockdown of Pou3f1 suppressed cell proliferation and increased 
      cell death in colon tumors. Both the in vivo and in vitro results showed that 
      Pou3f1 depletion reduced the production of proinflammation mediators. In 
      addition, ChIP and luciferase reporter assays demonstrated that Nfatc3 directly 
      bound with the Pou3f1 promoter to induce its expression. The effect of Nfatc3 on 
      the inflammatory response in macrophages was suppressed by Pou3f1 knockdown. 
      CONCLUSION: Overall, it outlines that Pou3f1 mediates the role of Nfatc3 in 
      regulating macrophage inflammation and carcinogenesis in UC-CRC development.
CI  - (c) 2022. The Author(s).
FAU - Lin, Yan
AU  - Lin Y
AD  - Department of Gastroenterology, Shengjing Hospital of China Medical University, 
      36 Sanhao Street, Heping District, 110004, Shenyang, China.
FAU - Wang, Dongxu
AU  - Wang D
AD  - Department of Gastroenterology, Shengjing Hospital of China Medical University, 
      36 Sanhao Street, Heping District, 110004, Shenyang, China.
FAU - Zhao, Hong
AU  - Zhao H
AD  - Department of Gastroenterology, Shengjing Hospital of China Medical University, 
      36 Sanhao Street, Heping District, 110004, Shenyang, China.
AD  - Department of Gastroenterology, The Second Affiliated Hospital of Shenyang 
      Medical College, Shenyang, China.
FAU - Li, Dongyue
AU  - Li D
AD  - Department of Gastroenterology, Shengjing Hospital of China Medical University, 
      36 Sanhao Street, Heping District, 110004, Shenyang, China.
AD  - Department of Respiratory, Ansteel Group General Hospital, Anshan, China.
FAU - Li, Xinning
AU  - Li X
AD  - Department of Gastroenterology, Shengjing Hospital of China Medical University, 
      36 Sanhao Street, Heping District, 110004, Shenyang, China.
AD  - Medical Oncology Ward, Tieling Central Hospital, Tieling, China.
FAU - Lin, Lianjie
AU  - Lin L
AD  - Department of Gastroenterology, Shengjing Hospital of China Medical University, 
      36 Sanhao Street, Heping District, 110004, Shenyang, China. leanlj13@yeah.net.
LA  - eng
PT  - Journal Article
DEP - 20220905
PL  - England
TA  - Cell Mol Biol Lett
JT  - Cellular & molecular biology letters
JID - 9607427
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Pou3f1 protein, mouse)
RN  - 0 (transcription factor NF-AT c3)
RN  - 132052-52-9 (Octamer Transcription Factor-6)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - Carcinogenesis
MH  - *Colitis-Associated Neoplasms
MH  - Dextran Sulfate/toxicity
MH  - Inflammation
MH  - Mice
MH  - NFATC Transcription Factors
MH  - Octamer Transcription Factor-6/*metabolism
PMC - PMC9446766
OTO - NOTNLM
OT  - Inflammation
OT  - Macrophage
OT  - Nfatc3
OT  - Pou3f1
OT  - Ulcerative colitis-associated colorectal cancer
COIS- The authors declare that they have no competing interests.
EDAT- 2022/09/06 06:00
MHDA- 2022/09/08 06:00
PMCR- 2022/09/05
CRDT- 2022/09/05 23:32
PHST- 2022/04/22 00:00 [received]
PHST- 2022/08/12 00:00 [accepted]
PHST- 2022/08/01 00:00 [revised]
PHST- 2022/09/05 23:32 [entrez]
PHST- 2022/09/06 06:00 [pubmed]
PHST- 2022/09/08 06:00 [medline]
PHST- 2022/09/05 00:00 [pmc-release]
AID - 10.1186/s11658-022-00374-0 [pii]
AID - 374 [pii]
AID - 10.1186/s11658-022-00374-0 [doi]
PST - epublish
SO  - Cell Mol Biol Lett. 2022 Sep 5;27(1):75. doi: 10.1186/s11658-022-00374-0.