Microrna-21 plays multiple oncometabolic roles in colitisassociated carcinoma and colorectal cancer via the pi3k/akt, stat3, and pdcd4/tnf-α signaling pathways in zebrafish

Chi Yu Lai, Kun Yun Yeh, Bi Feng Liu, Tzu Ming Chang, Chuan Hsun Chang, Yung Feng Liao, Yi Wen Liu, Guor Mour Her*

*此作品的通信作者

研究成果: Article同行評審

6 引文 斯高帕斯(Scopus)

摘要

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 IL6/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.

原文English
文章編號5565
期刊Cancers
13
發行號21
DOIs
出版狀態Published - 1 11月 2021

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