CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer.

Autor: Jiang T; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China., Wang H; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China., Liu L; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China., Song H; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China., Zhang Y; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China., Wang J; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China., Liu L; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China., Xu T; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China., Fan R; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China., Xu Y; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China., Wang S; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China., Shi L; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China., Zheng L; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, China., Wang R; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China. wangrenhao@xzhmu.edu.cn.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China. wangrenhao@xzhmu.edu.cn., Song J; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China. songjun@xzhmu.edu.cn.; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China. songjun@xzhmu.edu.cn.
Jazyk: angličtina
Zdroj: Molecular cancer [Mol Cancer] 2021 Dec 18; Vol. 20 (1), pp. 167. Date of Electronic Publication: 2021 Dec 18.
DOI: 10.1186/s12943-021-01474-9
Abstrakt: Background: Accumulating studies have revealed that aberrant expression of circular RNAs (circRNAs) is widely involved in the tumorigenesis and progression of malignant cancers, including colorectal cancer (CRC). Nevertheless, the clinical significance, levels, features, biological function, and molecular mechanisms of novel circRNAs in CRC remain largely unexplored.
Methods: CRC-related circRNAs were identified through bioinformatics analysis and verified in clinical specimens by qRT-PCR and in situ hybridization (ISH). Then, in vitro and in vivo experiments were performed to determine the clinical significance of, functional roles of, and clinical characteristics associated with circIL4R in CRC specimens and cells. Mechanistically, RNA pull-down, fluorescence in situ hybridization (FISH), luciferase reporter, and ubiquitination assays were performed to confirm the underlying mechanism of circIL4R.
Results: CircIL4R was upregulated in CRC cell lines and in sera and tissues from CRC patients and was positively correlated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that circIL4R promotes CRC cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. Mechanistically, circIL4R was regulated by TFAP2C and competitively interacted with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway and consequently facilitate CRC progression.
Conclusions: Our findings demonstrate that upregulation of circIL4R plays an oncogenic role in CRC progression and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment.
(© 2021. The Author(s).)
Databáze: MEDLINE
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