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环状GNB1通过调控miR-515-5p/miR-582-3p-XPR1轴促进神经胶质瘤干细胞的恶性表型。

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

作者信息

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

机构信息

Department of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.

Department of Radiology, The First Hospital of China Medical University, Shenyang, People's Republic of China.

出版信息

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

DOI:10.1186/s12935-023-02970-2
PMID:37407973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10320909/
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.

摘要

神经胶质瘤是最常见且侵袭性最强的原发性恶性脑肿瘤。环状RNA（circRNAs）和RNA结合蛋白（RBPs）已被证实可介导多种人类癌症中的不同生物学行为。因此，本研究的目的是探索一种名为circGNB1的新型环状RNA，并阐明其在功能表型中的相关分子机制，这可能是神经胶质瘤潜在的预后生物标志物和治疗方法。circGNB1在神经胶质瘤中上调，且与较差的预后密切相关。功能分析表明，circGNB1的过表达促进了神经胶质瘤干细胞（GSCs）的活力、增殖、侵袭和神经球形成。机制上，circGNB1通过吸附miR-515-5p和miR-582-3p上调癌基因XPR1的表达。后续实验证明，XPR1可通过上调IL6表达并激活JAK2/STAT3信号通路来促进GSCs的恶性表型。此外，RNA结合蛋白IGF2BP3可与circGNB1结合并维持其稳定性，从而增强circGNB1对GSCs的作用。我们的研究表明，circGNB1在促进神经胶质瘤的肿瘤发生和恶性进展中起关键作用，这为一种有前景的癌症生物标志物提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/787197ded5ab/12935_2023_2970_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/d1ff282862a1/12935_2023_2970_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/f762ab8a8295/12935_2023_2970_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/cea3a6dcc9ca/12935_2023_2970_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/924c279514c5/12935_2023_2970_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/241c766e6bad/12935_2023_2970_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/34e2325e2d29/12935_2023_2970_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/147f3ecb865f/12935_2023_2970_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/787197ded5ab/12935_2023_2970_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/d1ff282862a1/12935_2023_2970_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/f762ab8a8295/12935_2023_2970_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/cea3a6dcc9ca/12935_2023_2970_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/924c279514c5/12935_2023_2970_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/241c766e6bad/12935_2023_2970_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/34e2325e2d29/12935_2023_2970_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/147f3ecb865f/12935_2023_2970_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/10320909/787197ded5ab/12935_2023_2970_Fig8_HTML.jpg

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