Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma
Abstract Background To investigate the role of achaete-scute complex-like 2 (ASCL2) in stomach adenocarcinoma (STAD), we analyze whether ASCL2 suppression could retard cancer development and further observe the relevance between ASCL2 and inflammation via Toll-like receptor 4 (TLR4) activation in ST...
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Format: | Article |
Language: | English |
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BMC
2022-08-01
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Series: | World Journal of Surgical Oncology |
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Online Access: | https://doi.org/10.1186/s12957-022-02722-y |
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author | Enqi Zheng Zhun Cai Wangyong Li Chuandou Ni Qian Fang |
author_facet | Enqi Zheng Zhun Cai Wangyong Li Chuandou Ni Qian Fang |
author_sort | Enqi Zheng |
collection | DOAJ |
description | Abstract Background To investigate the role of achaete-scute complex-like 2 (ASCL2) in stomach adenocarcinoma (STAD), we analyze whether ASCL2 suppression could retard cancer development and further observe the relevance between ASCL2 and inflammation via Toll-like receptor 4 (TLR4) activation in STAD, both in vitro and in vivo. Methods Proliferation, development, inflammation, and apoptosis in STAD are observed using sh-ASCL2 lentivirus via TLR4 activation in vitro and in vivo. The relationship between ASCL2 and inflammation is analyzed. Western blotting of ASCL2 with the target protein of immune-associated cells is performed. The prognosis of STAD and associated ASCL2 mutation are analyzed. Results The ASCL2 level in STAD tumor tissues is increased, compared to normal tissues, and brings a worse prognosis. The ASCL2 shows a negative correlation with inflammation, and TLR4 reveals a positive correlation with gastric cancer. ASCL2 expression is high in MGC803 cells. Sh-ASCL2 could reduce STAD development by decreasing proliferation, tumor volume, and biomarker levels and increasing apoptosis in vitro and in vivo. The inflammatory role of ASCL2 is regulated through TLR4 activation. ASCL2 levels may be related to CNTNAP3, CLIP1, C9orf84, ARIH2, and IL1R2 mutations; positively correlated with M2 macrophage and T follicular helper cell levels; negatively correlated with neutrophil, dendritic cell, monocyte, CD8 T cell, and M1 macrophage levels; and involved in STAD prognosis. Conclusions The ASCL2 may adjust inflammation in STAD through TLR4 activation and may be associated with related immune cells. ASCL2 is possibly an upstream target factor of the TLR4 signaling pathway. |
first_indexed | 2024-04-11T14:24:14Z |
format | Article |
id | doaj.art-3f13760d2244491a815f7083a0b877ec |
institution | Directory Open Access Journal |
issn | 1477-7819 |
language | English |
last_indexed | 2024-04-11T14:24:14Z |
publishDate | 2022-08-01 |
publisher | BMC |
record_format | Article |
series | World Journal of Surgical Oncology |
spelling | doaj.art-3f13760d2244491a815f7083a0b877ec2022-12-22T04:18:54ZengBMCWorld Journal of Surgical Oncology1477-78192022-08-0120111310.1186/s12957-022-02722-yAchaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinomaEnqi Zheng0Zhun Cai1Wangyong Li2Chuandou Ni3Qian Fang4Department of General Surgery, The First People’s Hospital of WenlingDepartment of General Surgery, The First People’s Hospital of WenlingDepartment of General Surgery, The First People’s Hospital of WenlingDepartment of General Surgery, The First People’s Hospital of WenlingDepartment of General Surgery, The First People’s Hospital of WenlingAbstract Background To investigate the role of achaete-scute complex-like 2 (ASCL2) in stomach adenocarcinoma (STAD), we analyze whether ASCL2 suppression could retard cancer development and further observe the relevance between ASCL2 and inflammation via Toll-like receptor 4 (TLR4) activation in STAD, both in vitro and in vivo. Methods Proliferation, development, inflammation, and apoptosis in STAD are observed using sh-ASCL2 lentivirus via TLR4 activation in vitro and in vivo. The relationship between ASCL2 and inflammation is analyzed. Western blotting of ASCL2 with the target protein of immune-associated cells is performed. The prognosis of STAD and associated ASCL2 mutation are analyzed. Results The ASCL2 level in STAD tumor tissues is increased, compared to normal tissues, and brings a worse prognosis. The ASCL2 shows a negative correlation with inflammation, and TLR4 reveals a positive correlation with gastric cancer. ASCL2 expression is high in MGC803 cells. Sh-ASCL2 could reduce STAD development by decreasing proliferation, tumor volume, and biomarker levels and increasing apoptosis in vitro and in vivo. The inflammatory role of ASCL2 is regulated through TLR4 activation. ASCL2 levels may be related to CNTNAP3, CLIP1, C9orf84, ARIH2, and IL1R2 mutations; positively correlated with M2 macrophage and T follicular helper cell levels; negatively correlated with neutrophil, dendritic cell, monocyte, CD8 T cell, and M1 macrophage levels; and involved in STAD prognosis. Conclusions The ASCL2 may adjust inflammation in STAD through TLR4 activation and may be associated with related immune cells. ASCL2 is possibly an upstream target factor of the TLR4 signaling pathway.https://doi.org/10.1186/s12957-022-02722-yASCL2Stomach carcinomaTLR4Inflammation |
spellingShingle | Enqi Zheng Zhun Cai Wangyong Li Chuandou Ni Qian Fang Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma World Journal of Surgical Oncology ASCL2 Stomach carcinoma TLR4 Inflammation |
title | Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma |
title_full | Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma |
title_fullStr | Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma |
title_full_unstemmed | Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma |
title_short | Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma |
title_sort | achaete scute complex like 2 regulated inflammatory mechanism through toll like receptor 4 activating in stomach adenocarcinoma |
topic | ASCL2 Stomach carcinoma TLR4 Inflammation |
url | https://doi.org/10.1186/s12957-022-02722-y |
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