PMID- 37119608
OWN - NLM
STAT- MEDLINE
DCOM- 20230526
LR  - 20230526
IS  - 1618-0372 (Electronic)
IS  - 0065-1281 (Linking)
VI  - 125
IP  - 4
DP  - 2023 May
TI  - Dihydroartemisinin inhibited interleukin-18 expression by decreasing YAP1 in 
      hepatocellular carcinoma cells.
PG  - 152040
LID - S0065-1281(23)00046-6 [pii]
LID - 10.1016/j.acthis.2023.152040 [doi]
AB  - BACKGROUND: Yes-associated protein 1 (YAP1) is highly expressed in liver cancer 
      and has been used as an independent prognostic marker for hepatocellular 
      carcinoma (HCC), while inhibition of YAP1 slows down the progression of HCC. 
      Interleukin-18 (IL-18) also tends to be highly expressed in liver cancer. 
      Previous research has proved that dihydroartemisinin (DHA) plays an important 
      role in HCC treatment by reducing YAP1 expression. However, the relationship 
      between YAP1 and IL-18 has not been reported in HCC, especially during DHA 
      therapy. OBJECTIVE: The purpose of this study was to clarify the relationship 
      between YAP1 and IL-18 in HCC cells, and to explicit the role of IL-18 in the 
      treatment of HCC by DHA. METHODS AND RESULTS: We found that YAP1 and IL-18 were 
      highly expressed in patients with hepatocellular carcinoma by bioinformatics 
      analysis. Moreover, YAP1 was positively correlated with IL18 in liver cancer. 
      YAP1 and IL18 correlated with immune cell infiltration, notably T cell 
      exhaustion. YAP1 knockdown decreased IL-18 expression, while YAP1 overexpression 
      increased the IL-18 expression in HCC cells. DHA reduced IL-18 expression through 
      YAP1 in HCC cells. Further, DHA reduced the growth of Hepa1-6 cells subcutaneous 
      xenograft tumors by inhibiting the expression of YAP1 and IL-18. However, DHA 
      improved IL-18 in serum and adjacent tissues from DEN/TCPOBOP-induced liver tumor 
      model in C57BL/6 mice. CONCLUSION: YAP1 was positively correlated with IL-18 in 
      HCC. DHA reduced the expression of IL-18 by inhibiting YAP1 and plays a role in 
      the treatment of HCC. Our study suggested that IL-18 is a potential target for 
      the treatment of HCC, and DHA is a promising drug for HCC therapy. DATA 
      AVAILABILITY: The dataset that supports the findings of this study is available 
      from the corresponding author upon reasonable request.
CI  - Copyright (c) 2023. Published by Elsevier GmbH.
FAU - Gong, Yi
AU  - Gong Y
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China.
FAU - Peng, Qing
AU  - Peng Q
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China.
FAU - Gao, Yuting
AU  - Gao Y
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China; School of Basic Medical Sciences, Shanxi University 
      of Chinese Medicine, Jinzhong 030619, China.
FAU - Yang, Jiali
AU  - Yang J
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China.
FAU - Lu, Junlan
AU  - Lu J
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China.
FAU - Zhang, Yuman
AU  - Zhang Y
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China.
FAU - Yang, Yanguang
AU  - Yang Y
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China.
FAU - Liang, Hua
AU  - Liang H
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China.
FAU - Yue, Yuan
AU  - Yue Y
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China.
FAU - Shi, Xinli
AU  - Shi X
AD  - Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 
      Shijiazhuang 050200, China. Electronic address: sxlsunshine@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20230427
PL  - Germany
TA  - Acta Histochem
JT  - Acta histochemica
JID - 0370320
RN  - 6A9O50735X (artenimol)
RN  - 0 (Interleukin-18)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - *Carcinoma, Hepatocellular/drug therapy/metabolism
MH  - *Liver Neoplasms/metabolism
MH  - Interleukin-18/metabolism/therapeutic use
MH  - Cell Line, Tumor
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Adaptor Proteins, Signal Transducing/genetics
MH  - Transcription Factors/metabolism
MH  - Gene Expression Regulation, Neoplastic
OTO - NOTNLM
OT  - Dihydroartemisinin
OT  - Hepatocellular carcinoma
OT  - IL-18
OT  - Tumor microenvironment
OT  - YAP1
COIS- Declaration of Competing Interest The author stated that there were no competing 
      interests.
EDAT- 2023/04/30 00:42
MHDA- 2023/05/26 06:42
CRDT- 2023/04/29 18:03
PHST- 2022/12/12 00:00 [received]
PHST- 2023/04/22 00:00 [revised]
PHST- 2023/04/22 00:00 [accepted]
PHST- 2023/05/26 06:42 [medline]
PHST- 2023/04/30 00:42 [pubmed]
PHST- 2023/04/29 18:03 [entrez]
AID - S0065-1281(23)00046-6 [pii]
AID - 10.1016/j.acthis.2023.152040 [doi]
PST - ppublish
SO  - Acta Histochem. 2023 May;125(4):152040. doi: 10.1016/j.acthis.2023.152040. Epub 
      2023 Apr 27.