PMID- 35640269
OWN - NLM
STAT- MEDLINE
DCOM- 20220922
LR  - 20221013
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 43
IP  - 8
DP  - 2022 Sep 19
TI  - Low G9a expression is a tumor progression factor of colorectal cancer via IL-8 
      promotion.
PG  - 797-807
LID - 10.1093/carcin/bgac050 [doi]
AB  - The histone methyltransferase G9a is expressed in various types of cancer cells, 
      including colorectal cancer (CRC) cells. Interleukin 8 (IL)-8, also known as 
      C-X-C motif chemokine ligand 8 (CXCL8), is a chemokine that plays a pleiotropic 
      function in the regulation of inflammatory responses and cancer development. 
      Here, we examined the relationship between G9a and IL-8 and the clinical 
      relevance of this association. We immunohistochemically analyzed 235 resected CRC 
      samples to correlate clinical features. Samples with high G9a expression had 
      better overall survival and relapse-free survival than those with low G9a 
      expression. Univariate and multivariate analyses demonstrated that low G9a 
      expression remained a significant independent prognostic factor for increased 
      disease recurrence and decreased survival (P < 0.05). G9a was expressed at high 
      levels in commercially available CRC cell lines HCT116 and HT29. Knockdown of G9a 
      by siRNA, shRNA or the G9a-specific inhibitor BIX01294 upregulated IL-8 
      expression. The number of spheroids was significantly increased in HCT116 cells 
      with stably suppressed G9a expression, and the number of spheroids was 
      significantly decreased in HCT116 cells with stably suppressed IL-8 expression. 
      Thus, the suppression of IL-8 by G9a may result in a better prognosis in CRC 
      cases with high G9a expression. Furthermore, G9a may suppress cancer stemness and 
      increase chemosensitivity by controlling IL-8. Therefore, G9a is a potential 
      novel marker for predicting CRC prognosis, and therapeutic targeting of G9a in 
      CRC should be controversial.
CI  - (c) The Author(s) 2022. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Ichikawa, Yoshitoshi
AU  - Ichikawa Y
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Takahashi, Hidekazu
AU  - Takahashi H
AUID- ORCID: 0000-0003-2878-5391
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Chinen, Yoshinao
AU  - Chinen Y
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Arita, Asami
AU  - Arita A
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Sekido, Yuki
AU  - Sekido Y
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Hata, Tsuyoshi
AU  - Hata T
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Ogino, Takayuki
AU  - Ogino T
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Miyoshi, Norikatsu
AU  - Miyoshi N
AUID- ORCID: 0000-0003-1113-8884
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Uemura, Mamoru
AU  - Uemura M
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Yamamoto, Hirofumi
AU  - Yamamoto H
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Mizushima, Tsunekazu
AU  - Mizushima T
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Doki, Yuichiro
AU  - Doki Y
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Eguchi, Hidetoshi
AU  - Eguchi H
AUID- ORCID: 0000-0002-2318-1129
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Histocompatibility Antigens)
RN  - 0 (Interleukin-8)
RN  - 0 (Ligands)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.1.1.- (Histone Methyltransferases)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - *Colorectal Neoplasms/pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - *Histocompatibility Antigens/genetics/metabolism
MH  - Histone Methyltransferases/genetics/metabolism
MH  - Histone-Lysine N-Methyltransferase/genetics/metabolism
MH  - Humans
MH  - Interleukin-8/genetics
MH  - Ligands
MH  - RNA, Small Interfering
EDAT- 2022/06/01 06:00
MHDA- 2022/09/23 06:00
CRDT- 2022/05/31 17:32
PHST- 2021/11/22 00:00 [received]
PHST- 2022/05/15 00:00 [revised]
PHST- 2022/05/26 00:00 [accepted]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/09/23 06:00 [medline]
PHST- 2022/05/31 17:32 [entrez]
AID - 6594761 [pii]
AID - 10.1093/carcin/bgac050 [doi]
PST - ppublish
SO  - Carcinogenesis. 2022 Sep 19;43(8):797-807. doi: 10.1093/carcin/bgac050.