Yang Xuanyong, Liu Yue, Zhou Xinhui, Chen Kang, Xu Jiang, Xu Shan
Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, China.
Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, China; Institute of Medicine, Nanchang University, China.
Transl Oncol. 2022 Nov;25:101515. doi: 10.1016/j.tranon.2022.101515. Epub 2022 Sep 7.
Noncoding RNAs (ncRNAs) play important roles in cancer biology, providing potential targets for cancer intervention. As a new class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified in cell development and function, and certain types of pathological responses contribute to cancer progression, including glioblastoma. However, the potential mechanisms underlying the relationship between circRNAs and glioblastoma progression are still largely unknown. Methods: The expression and roles of circular RNA 0010117 (circ-0010117) were examined in vitro and in vivo. Quantitative RT‒PCR and western blotting were used to measure the expression of circRNA, miRNA, each gene, or related proteins. Cell biology experiments were performed to detect the biological function of circ-0010117 in glioblastoma cell lines. Moreover, bioinformatics analysis, luciferase reporter assays, and functional complementation analysis were carried out to investigate the target genes. Tumorigenesis was also evaluated by xenografting cells into nude mice. In this study, we found that circ-0010117 is downregulated in glioblastoma compared with corresponding paratumoural tissues. Subsequently, we observed that circ-0010117 can regulate aggressiveness in glioblastoma cells through miR-6779-5p. Furthermore, SPEN was verified as a direct target of miR-6779-5p and contributes to the circ-0010117 regulatory network. In addition, we identified that overexpression of circ-0010117 can suppress tumorigenesis in nude mice. Our findings indicate that circular RNA 0010117 promotes the aggressive behavior of glioblastoma by regulating the miRNA-6779-5p/SPEN axis. Our results provide a rationale for the use of circ-0010117 as a novel potential therapeutic target in glioblastoma.
非编码RNA（ncRNAs）在癌症生物学中发挥着重要作用，为癌症干预提供了潜在靶点。作为一类新型的内源性非编码RNA，环状RNA（circRNAs）最近在细胞发育和功能中被发现，某些类型的病理反应促进癌症进展，包括胶质母细胞瘤。然而，circRNAs与胶质母细胞瘤进展之间关系的潜在机制仍 largely 未知。方法：在体外和体内检测环状RNA 0010117（circ-0010117）的表达和作用。定量RT-PCR和蛋白质印迹法用于测量circRNA、miRNA、每个基因或相关蛋白质的表达。进行细胞生物学实验以检测circ-0010117在胶质母细胞瘤细胞系中的生物学功能。此外，进行生物信息学分析、荧光素酶报告基因测定和功能互补分析以研究靶基因。还通过将细胞异种移植到裸鼠中来评估肿瘤发生。在本研究中，我们发现与相应的瘤旁组织相比，circ-0010117在胶质母细胞瘤中表达下调。随后，我们观察到circ-0010117可通过miR-6779-5p调节胶质母细胞瘤细胞的侵袭性。此外，SPEN被证实为miR-6779-5p的直接靶标，并参与circ-0010117调控网络。此外，我们发现circ-0010117的过表达可抑制裸鼠中的肿瘤发生。我们的研究结果表明，环状RNA 0010117通过调节miRNA-6779-5p/SPEN轴促进胶质母细胞瘤的侵袭行为。我们的结果为将circ-0010117用作胶质母细胞瘤的新型潜在治疗靶点提供了理论依据。
