Department of Neurosurgery, Ren Ji Hospital, Schoolof Medicine, Shanghai Jiao Tong University, Shanghai, China.
Institute of Neuroscience, State Kay Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Cancer Med. 2018 Dec;7(12):6147-6157. doi: 10.1002/cam4.1613. Epub 2018 Nov 6.
Circular RNAs (circRNAs) have been demonstrated to be involved in various biological processes. Nevertheless, the function of circRNAs in medulloblastoma (MB) is still unknown. The present study aimed to investigate the expression profiles of circRNAs and related mechanisms for regulating the proliferation and growth of tumor cells in MB. The expression profiles of circRNAs were screened from four normal cerebellum and four MB samples using a HiSeq Sequencer. Bioinformatic analysis was employed to predict the interaction between circRNAs and mRNAs in MB. Subsequently, the expression levels of eight differential circRNAs [circ-SKA3 (hsa_circ_0029696), circ-DTL (hsa_circ_0000179), circ-CRTAM, circ-MAP3K5 (hsa_circ_0006856), circ-RIMS1-1 (hsa_circ_0132250), circ-RIMS1-2 (hsa_circ_0076967), circ-FLT3-1 (hsa_circ_0100165), and circ-FLT3-2 (hsa_circ_0100168)] were validated using quantitative reverse transcription-polymerase chain reaction. Moreover, circ-SKA3 and circ-DTL were silenced using small interfering RNAs and their host genes were overexpressed to investigate their role in the pathogenesis of MB. A total of 33 circRNAs were found to be differentially expressed in MB tissues (fold change ≥ 2.0, FDR <0.05), of which three were upregulated and 30 were downregulated; six circRNAs were experimentally validated successfully. Upregulated circ-SKA3 and circ-DTL promoted the proliferation migration and invasion in vitro by regulating the expression of host genes. This novel study exploited the profiling of circRNAs in MB and demonstrated that circ-SKA3 and circ-DTL were crucial in the tumorigenesis and development of MB and might be considered as novel and potential biomarkers for the diagnosis and new targets for the intervention of MB.
环状 RNA（circRNAs）已被证明参与了多种生物学过程。然而，circRNAs 在髓母细胞瘤（MB）中的功能仍不清楚。本研究旨在探讨 circRNAs 的表达谱及其相关机制，以调节 MB 中肿瘤细胞的增殖和生长。使用 HiSeq 测序仪从四个正常小脑和四个 MB 样本中筛选 circRNAs 的表达谱。生物信息学分析用于预测 MB 中 circRNAs 与 mRNAs 之间的相互作用。随后，使用定量逆转录聚合酶链反应验证了八个差异表达 circRNAs [circ-SKA3（hsa_circ_0029696）、circ-DTL（hsa_circ_0000179）、circ-CRTAM、circ-MAP3K5（hsa_circ_0006856）、circ-RIMS1-1（hsa_circ_0132250）、circ-RIMS1-2（hsa_circ_0076967）、circ-FLT3-1（hsa_circ_0100165）和 circ-FLT3-2（hsa_circ_0100168）] 的表达水平。此外，使用小干扰 RNA 沉默 circ-SKA3 和 circ-DTL，并过表达其宿主基因，以研究它们在 MB 发病机制中的作用。在 MB 组织中发现 33 个 circRNAs 表达差异（倍数变化≥2.0，FDR<0.05），其中 3 个上调，30 个下调；六个 circRNAs 成功进行了实验验证。上调的 circ-SKA3 和 circ-DTL 通过调节宿主基因的表达促进了体外增殖、迁移和侵袭。这项新的研究利用 MB 中 circRNAs 的分析，表明 circ-SKA3 和 circ-DTL 在 MB 的肿瘤发生和发展中至关重要，可能被视为诊断 MB 的新的潜在生物标志物和干预 MB 的新靶点。
