FUS/circZEB1/miR-128-3p/LBH feedback loop contributes to the malignant phenotype of GSCs via TNF-α-mediated NF-κB signaling pathway

Guoqing Zhang; Yang Jiang; Zhichao Wang; Zhengting Guo; Jinpeng Hu; Xinqiao Li; Yongfeng Wang; Zhitao Jing

doi:10.1186/s12935-024-03526-8

FUS/circZEB1/miR-128-3p/LBH feedback loop contributes to the malignant phenotype of GSCs via TNF-α-mediated NF-κB signaling pathway

Cancer Cell Int. 2024 Nov 7;24(1):365. doi: 10.1186/s12935-024-03526-8.

Authors

Guoqing Zhang^#¹, Yang Jiang^#², Zhichao Wang^#³, Zhengting Guo¹, Jinpeng Hu¹, Xinqiao Li¹, Yongfeng Wang⁴, Zhitao Jing⁵

Affiliations

¹ Department of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China.
² Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 200072, Shanghai, People's Republic of China.
³ Department of Neurosurgery, The People's Hospital of China Medical University, Shenyang, 110067, China.
⁴ Department of Radiology, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China. wyf1208@163.com.
⁵ Department of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, China. jingzhitao@hotmail.com.

^# Contributed equally.

Abstract

Glioblastoma (GBM) is the most lethal and common primary tumor of central nervous system with a poor prognosis. Glioma stem cells (GSCs) are particularly significant in GBM proliferation, invasion, self-renewal and recurrence. Circular RNAs (circRNAs) play important roles in various physiological and pathological processes, including regulating the biological behavior of GBM. Therefore, discovering novel circRNAs related to GSCs may contribute to a promising approach for treatment of GBM. Herein, we find out a novel circRNA termed circZEB1 with a high expression in glioma. Limb-bud and heart (LBH) is a transcription cofactor and promotes glioma stem cell tumorigenicity in our study. Mechanistically, circZEB1 can upregulate the expression of transcription cofactor LBH via sponging miR-128-3p in GSCs. LBH can facilitate the expression of tumor necrosis factor-α (TNF-α), thus activating the NF-κB signaling pathway to promote the glioma progression. Meanwhile, LBH can also upregulate the RNA binding protein Fused in Sarcoma (FUS) expression, which can bind to and maintain the stability of circZEB1. A positive feedback loop is formed among FUS, circZEB1, miR-128-3p and LBH in GSCs. Our study uncovers a critical role of circZEB1 and provides a novel biomarker for treating GBM.

Keywords: CircZEB1; Glioblastoma; Glioma stem cells; Limb-bud and heart; NF-κB signaling pathway.

Abstract

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