PUBLICATION
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
- Authors
- Lai, C.Y., Yeh, K.Y., Liu, B.F., Chang, T.M., Chang, C.H., Liao, Y.F., Liu, Y.W., Her, G.M.
- ID
- ZDB-PUB-211116-18
- Date
- 2021
- Source
- Cancers 13(21): (Journal)
- Registered Authors
- Her, Guor Muor, Liao, Yun-Feng
- Keywords
- colitis-associated colorectal cancer (CAC), colorectal cancer (CRC), inflammatory bowel disease (IBD), microRNAs, zebrafish
- MeSH Terms
- none
- PubMed
- 34771727 Full text @ Cancers
Citation
Lai, C.Y., Yeh, K.Y., Liu, B.F., Chang, T.M., Chang, C.H., Liao, Y.F., Liu, Y.W., Her, G.M. (2021) 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. Cancers. 13(21):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping