ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells

Abstract Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the...

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Main Authors: Ting Lin, Shuxian Zhang, Yi Tang, Ming Xiao, Ming Li, Hanjuan Gong, Hailun Xie, Yalan Wang
Format: Article
Language:English
Published: BMC 2024-03-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-024-12120-0
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author Ting Lin
Shuxian Zhang
Yi Tang
Ming Xiao
Ming Li
Hanjuan Gong
Hailun Xie
Yalan Wang
author_facet Ting Lin
Shuxian Zhang
Yi Tang
Ming Xiao
Ming Li
Hanjuan Gong
Hailun Xie
Yalan Wang
author_sort Ting Lin
collection DOAJ
description Abstract Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.
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spelling doaj.art-ed6f28b475d54a0c983b517e9c18c50a2024-03-24T12:23:31ZengBMCBMC Cancer1471-24072024-03-0124111310.1186/s12885-024-12120-0ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cellsTing Lin0Shuxian Zhang1Yi Tang2Ming Xiao3Ming Li4Hanjuan Gong5Hailun Xie6Yalan Wang7Department of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical UniversityDepartment of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical UniversityDepartment of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical UniversityDepartment of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical UniversityDepartment of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical UniversityDepartment of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical UniversityDepartment of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical UniversityDepartment of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical UniversityAbstract Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.https://doi.org/10.1186/s12885-024-12120-0ART1Cell proliferationColorectal cancergp130IL-6
spellingShingle Ting Lin
Shuxian Zhang
Yi Tang
Ming Xiao
Ming Li
Hanjuan Gong
Hailun Xie
Yalan Wang
ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells
BMC Cancer
ART1
Cell proliferation
Colorectal cancer
gp130
IL-6
title ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells
title_full ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells
title_fullStr ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells
title_full_unstemmed ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells
title_short ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells
title_sort art1 knockdown decreases the il 6 induced proliferation of colorectal cancer cells
topic ART1
Cell proliferation
Colorectal cancer
gp130
IL-6
url https://doi.org/10.1186/s12885-024-12120-0
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