Background: Circular RNAs (circRNAs) are a newly discovered type of non-coding RNA, which have been demonstrated to act as microRNA (miRNA) “sponges” to modulate gene expression. Emerging evidence has confirmed that circRNAs take part in many biological processes in a variety of malignant tumors, including gliomas, suggesting that they could serve as biomarkers or therapeutic targets for tumors. The purpose of this study was to explore the roles of circRNAs in gliomas and to provide valuable clues for clinical diagnosis and treatment.

Methods: RNA-seq data with poly(A)-/RNase R treatment was employed to investigate the expression profiles of circRNAs in tumor and paracancerous tissues derived from glioma patients. CircAST was used for full-length circRNA reconstruction and quantification. Bioinformatics analyses, including GO enrichment and KEGG pathway analyses, were performed to reveal the potential biological process and pathways of their host genes. A circRNA-miRNA interaction network was constructed to depict the interactions of the dysregulated circRNA transcripts with miRNAs.

Results: A total of 20,474 circular transcripts that originated from 16,022 circRNAs were successfully reconstructed in the samples. We detected 646 upregulated and 112 downregulated circular transcripts in tumor tissues compared with paracancerous tissues. GO analysis revealed that their host genes might be related to positive regulation of GTPase activity, regulation of synaptic transmission, and glutamatergic and dendrite morphogenesis in the cytoplasm and cytosol. KEGG pathway analysis showed that the glutamatergic synapse, neurotrophin signaling pathway, and ErbB signaling pathway might be linked to the occurrence and development of gliomas.

Conclusion: Our study revealed a comprehensive profile of differentially expressed circRNA transcripts in gliomas, indicating that aberrantly expressed circRNAs might play important roles in the occurrence and development of human gliomas.

背景：环状RNA（circRNA）是一种新发现的非编码RNA，已被证明可作为微RNA（miRNA）“海绵”来调节基因表达。新出现的证据证实，circRNAs参与了包括胶质瘤在内的多种恶性肿瘤的许多生物学过程，表明它们可以作为肿瘤的生物标志物或治疗靶点。本研究旨在探讨circRNAs在胶质瘤中的作用，为临床诊治提供有价值的线索。

方法：采用 poly(A)-/RNase R 处理的 RNA-seq 数据来研究 circRNAs 在来自神经胶质瘤患者的肿瘤和癌旁组织中的表达谱。CircAST 用于全长 circRNA 重建和定量。进行生物信息学分析，包括 GO 富集和 KEGG 通路分析，以揭示其宿主基因的潜在生物学过程和通路。构建了一个 circRNA-miRNA 相互作用网络来描述失调的 circRNA 转录本与 miRNA 的相互作用。

结果：在样本中成功重建了来自 16,022 个 circRNA 的 20,474 个环状转录本。与癌旁组织相比，我们在肿瘤组织中检测到 646 个上调和 112 个下调的环状转录本。GO分析表明，它们的宿主基因可能与GTPase活性的正调控、突触传递的调控以及细胞质和细胞质中的谷氨酸能和树突形态发生有关。KEGG通路分析表明，谷氨酸能突触、神经营养因子信号通路和ErbB信号通路可能与胶质瘤的发生发展有关。

结论：我们的研究揭示了神经胶质瘤中差异表达的 circRNA 转录本的综合特征，表明异常表达的 circRNA 可能在人类神经胶质瘤的发生和发展中发挥重要作用。