Dysregulated circular RNAs in medulloblastoma regulate proliferation and growth of tumor cells via host genes.
Dysregulated circular RNAs in medulloblastoma regulate proliferation and growth of tumor cells via host genes.
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髓母细胞瘤中失调的环状 RNA 通过宿主基因调节肿瘤细胞的增殖和生长。
DOI：
10.1002/cam4.1613
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发表时间：
2018-12
期刊：
影响因子：
4
通讯作者：
Zhang XH
中科院分区：
文献类型：
--
作者：
Lv T;Miao YF;Jin K;Han S;Xu TQ;Qiu ZL;Zhang XH
环状RNA（circRNA）已被证明参与各种生物过程。然而，circRNA在髓母细胞瘤（MB）中的功能仍然未知。本研究旨在探讨MB中circRNA的表达谱及其调控肿瘤细胞增殖和生长的相关机制。使用HiSeq测序仪从四个正常小脑和四个MB样品中筛选circRNA的表达谱。采用生物信息学分析来预测MB中circRNA和mRNA之间的相互作用。随后，八种不同的circRNA [circ-SKA 3]的表达水平（hsa_circ_0029696），circ-DTL（hsa_circ_0000179），circ‐CRTAM，circ‐MAP3K5（hsa_circ_0006856），circ-RIMS 1 - 1（hsa_circ_0132250）、circ‐ RIMS 1 ‐2（hsa_circ_0076967）、circ‐ FLT 3 ‐1（hsa_circ_0100165）和circ‐ FLT 3 ‐2（hsa_circ_0100168）]使用定量逆转录-聚合酶链反应进行验证。此外，使用小干扰RNA沉默circ‐ SKA 3和circ‐DTL，并过表达其宿主基因，以研究其在MB发病机制中的作用。共发现33种circRNA在MB组织中差异表达（倍数变化≥ 2.0，FDR <0.05），其中3种上调，30种下调; 6种circRNA经实验成功验证。circ‐ SKA 3和circ‐DTL的表达上调可通过调节宿主基因的表达促进细胞的体外增殖、迁移和侵袭。这项新研究利用了MB中的circRNA谱，并证明了circ-SKA 3和circ-DTL在MB的肿瘤发生和发展中至关重要，并可能被认为是诊断的新型潜在生物标志物和干预MB的新靶点。
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.
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影响因子：
--
作者：
Chuang TP;Wang JY;Jao SW;Wu CC;Chen JH;Hsiao KH;Lin CY;Chen SH;Su SY;Chen YJ;Chen YT;Wu DC;Li LH
通讯作者：
Li LH
影响因子：
8
作者：
Mackintosh, C.;Ordonez, J. L.;de Alava, E.
通讯作者：
de Alava, E.
影响因子：
1.9
作者：
Bansal, Lalit R.;Belair, Jeffrey;Zuccoli, Giulio
通讯作者：
Zuccoli, Giulio
影响因子：
4.4
作者：
Jiao X;Hooper SD;Djureinovic T;Larsson C;Wärnberg F;Tellgren-Roth C;Botling J;Sjöblom T
通讯作者：
Sjöblom T
影响因子：
3.9
作者：
Ohtsuka M;Ling H;Doki Y;Mori M;Calin GA
通讯作者：
Calin GA