Circ_0004585 Facilitates Tumorigenesis of Colorectal Cancer Modulating the MiR-338-3p/ZFX Axis and Activating the MEK/ERK Pathway

Overview

Journal Cell Mol Bioeng

Publisher Springer

Specialty Biomedical Engineering

Date 2023 Apr 25

PMID 37096071

Authors

Zenghai Lin

Jianwei Lin

Affiliations

Soon will be listed here.

Abstract

Background: Colorectal cancer (CRC) is a common malignant tumor in the digestive tract. Circular RNAs (circRNAs) have been identified as crucial regulators of tumorigenesis. However, the role and potential mechanism of circ_0004585 in CRC are poorly understood.

Methods: The expression of circ_0004585, microRNA-338-3p (miR-338-3p), and zinc finger protein X-linked (ZFX) was detected by quantitative real-time PCR and Western blot. Cell proliferation, cell cycle arrest, apoptosis, and angiogenesis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry and tube formation assays. Western blot assay was applied to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins and MEK/ERK signaling pathway-related proteins. A xenograft model was used to analyze tumor growth . The targeted relationship between miR-338-3p and circ_0004585/ZFX was verified by a dual-luciferase reporter assay.

Results: Circ_0004585 and ZFX were up-regulated, while miR-338-3p was down-regulated in CRC tissues and cells. Silencing of circ_0004585 inhibited proliferation, angiogenesis, and EMT and triggered apoptosis in CRC cells. Consistently, circ_0004585 depletion blocked tumor growth . Circ_0004585 contributed to CRC cell development sequestering miR-338-3p. Also, miR-338-3p hindered the malignant progression of CRC cells by targeting ZFX. Circ_0004585 activated MEK/ERK pathway regulating ZFX.

Conclusion: Circ_0004585 facilitated CRC progression through modulating miR-338-3p/ZFX/MEK/ERK pathway, which might provide a potential therapeutic target for CRC.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-022-00756-6.

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