MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, especially microRNAs. MicroRNA-21 (miR-21) is amongs...

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Autores principales:	Chi-Yu Lai, Kun-Yun Yeh, Bi-Feng Liu, Tzu-Ming Chang, Chuan-Hsun Chang, Yung-Feng Liao, Yi-Wen Liu, Guor Mour Her
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microRNAs colorectal cancer (CRC) inflammatory bowel disease (IBD) colitis-associated colorectal cancer (CAC) zebrafish Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ebbf53944c8c49cdae936984bbdbeb48
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spelling	oai:doaj.org-article:ebbf53944c8c49cdae936984bbdbeb482021-11-11T15:35:20ZMicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish10.3390/cancers132155652072-6694https://doaj.org/article/ebbf53944c8c49cdae936984bbdbeb482021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5565https://doaj.org/toc/2072-6694Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, especially microRNAs. MicroRNA-21 (miR-21) is amongst the most frequently upregulated microRNAs in inflammatory responses and cancer development. miR-21 has become a target for genetic and pharmacological regulation in various diseases. However, the association between inflammation and tumorigenesis in the gut is largely unknown. Hence, in this study, we generated a zebrafish model (ImiR-21) with inducible overexpression of miR-21 in the intestine. The results demonstrate that miR-21 can induce CRC or colitis-associated cancer (CAC) in ImiR-21 through the PI3K/AKT, PDCD4/TNF-α, and IL-6/STAT3 signaling network. miR-21 activated the PI3K/AKT and NF-κB signaling pathways, leading to initial inflammation; thereafter, miR-21 and TNF-α repressed PDCD4 and its tumor suppression activity. Eventually, active STAT3 stimulated a strong inflammatory response and activated the invasion/metastasis process of tumor cells. Hence, our findings indicate that miR-21 is critical for the development of CRC/CAC via the PI3K/AKT, STAT3, and PDCD4/TNF-α signaling networks.Chi-Yu LaiKun-Yun YehBi-Feng LiuTzu-Ming ChangChuan-Hsun ChangYung-Feng LiaoYi-Wen LiuGuor Mour HerMDPI AGarticlemicroRNAscolorectal cancer (CRC)inflammatory bowel disease (IBD)colitis-associated colorectal cancer (CAC)zebrafishNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5565, p 5565 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microRNAs colorectal cancer (CRC) inflammatory bowel disease (IBD) colitis-associated colorectal cancer (CAC) zebrafish Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	microRNAs colorectal cancer (CRC) inflammatory bowel disease (IBD) colitis-associated colorectal cancer (CAC) zebrafish Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Chi-Yu Lai Kun-Yun Yeh Bi-Feng Liu Tzu-Ming Chang Chuan-Hsun Chang Yung-Feng Liao Yi-Wen Liu Guor Mour Her MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish
description	Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, especially microRNAs. MicroRNA-21 (miR-21) is amongst the most frequently upregulated microRNAs in inflammatory responses and cancer development. miR-21 has become a target for genetic and pharmacological regulation in various diseases. However, the association between inflammation and tumorigenesis in the gut is largely unknown. Hence, in this study, we generated a zebrafish model (ImiR-21) with inducible overexpression of miR-21 in the intestine. The results demonstrate that miR-21 can induce CRC or colitis-associated cancer (CAC) in ImiR-21 through the PI3K/AKT, PDCD4/TNF-α, and IL-6/STAT3 signaling network. miR-21 activated the PI3K/AKT and NF-κB signaling pathways, leading to initial inflammation; thereafter, miR-21 and TNF-α repressed PDCD4 and its tumor suppression activity. Eventually, active STAT3 stimulated a strong inflammatory response and activated the invasion/metastasis process of tumor cells. Hence, our findings indicate that miR-21 is critical for the development of CRC/CAC via the PI3K/AKT, STAT3, and PDCD4/TNF-α signaling networks.
format	article
author	Chi-Yu Lai Kun-Yun Yeh Bi-Feng Liu Tzu-Ming Chang Chuan-Hsun Chang Yung-Feng Liao Yi-Wen Liu Guor Mour Her
author_facet	Chi-Yu Lai Kun-Yun Yeh Bi-Feng Liu Tzu-Ming Chang Chuan-Hsun Chang Yung-Feng Liao Yi-Wen Liu Guor Mour Her
author_sort	Chi-Yu Lai
title	MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish
title_short	MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish
title_full	MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish
title_fullStr	MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish
title_full_unstemmed	MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish
title_sort	microrna-21 plays multiple oncometabolic roles in colitis-associated carcinoma and colorectal cancer via the pi3k/akt, stat3, and pdcd4/tnf-α signaling pathways in zebrafish
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ebbf53944c8c49cdae936984bbdbeb48
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MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish

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