CircGNB1 facilitates the malignant phenotype of GSCs by regulating miR-515-5p/miR-582-3p-XPR1 axis

Jinpeng Hu; Guoqing Zhang; Yongfeng Wang; Kai Xu; Lian Chen; Gang Luo; Jinkun Xu; Hao Li; Dongmei Pei; Xiang Zhao; Zhengting Guo; Xinqiao Li; Shengliang Zong; Yang Jiang; Zhitao Jing

doi:10.1186/s12935-023-02970-2

CircGNB1 facilitates the malignant phenotype of GSCs by regulating miR-515-5p/miR-582-3p-XPR1 axis

Cancer Cell Int. 2023 Jul 5;23(1):132. doi: 10.1186/s12935-023-02970-2.

Authors

Jinpeng Hu^#¹, Guoqing Zhang^#¹, Yongfeng Wang^#², Kai Xu¹, Lian Chen¹, Gang Luo³, Jinkun Xu¹, Hao Li¹, Dongmei Pei⁴, Xiang Zhao¹, Zhengting Guo¹, Xinqiao Li¹, Shengliang Zong¹, Yang Jiang⁵, Zhitao Jing⁶

Affiliations

¹ Department of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
² Department of Radiology, The First Hospital of China Medical University, Shenyang, People's Republic of China.
³ Liaoning Maternal and Child Health Hospital, No. 240 Shayang Road, Shenyang, 110005, People's Republic of China.
⁴ Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
⁵ Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China. windjy0523@qq.com.
⁶ Department of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. jingzhitao@hotmail.com.

^# Contributed equally.

Abstract

Glioma is the most common and aggressive primary malignant brain tumor. Circular RNAs (circRNAs) and RNA-binding proteins (RBPs) have been verified to mediate diverse biological behaviors in various human cancers. Therefore, the aim of this study was to explore a novel circRNA termed circGNB1 and elucidate relative molecular mechanism in functional phenotypes, which might be a potential prognostic biomarker and therapeutic approach for glioma. CircGNB1 was upregulated in glioma and closely associated with the low poor prognosis. Functional assays demonstrated that circGNB1 overexpression promoted glioma stem cells (GSCs) viability proliferation, invasion, and neurosphere formation. Mechanistically, circGNB1 upregulated the expression of oncogene XPR1 via sponging miR-515-5p and miR-582-3p. The following experiments proved XPR1 could promote the malignant phenotype of GSCs via upregulating IL6 expression and activating JAK2/STAT3 signaling. Moreover, the RNA binding protein IGF2BP3 could bind to and maintain the stability of circGNB1, thus promoting the effects of circGNB1 on GSCs. Our study reveals that circGNB1 plays a crucial role in promoting tumorigenesis and malignant progression in glioma, which provides a promising cancer biomarker.

Keywords: Glioma; Glioma stem cells; Malignant progression; XPR1; circGNB1.

Abstract

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