O'Leary Valerie Bríd, Smida Jan, Matjanovski Martina, Brockhaus Corinna, Winkler Klaudia, Moertl Simone, Ovsepian Saak Victor, Atkinson Michael John
Institute of Radiation Biology, Helmholtz Zentrum Munich - German Research Center for Environmental Health, Neuherberg, Germany.
Institute of Biological and Medical Imaging, Helmholtz Zentrum Munich - German Research Center for Environmental Health, Neuherberg, Germany.
Oncotarget. 2017 Jul 13;8(45):78397-78409. doi: 10.18632/oncotarget.19228. eCollection 2017 Oct 3.
Generated by Quaking (QKI), circular RNAs (circRNAs) are newly recognised non-coding RNA (ncRNA) members characterised by tissue specificity, increased stability and enrichment within exosomes. Studies have shown that ionizing radiation (IR) can influence ncRNA transcription. However, it is unknown whether circRNAs or indeed QKI are regulated by IR. Microarray circRNA profiling and next generation sequencing revealed that circRNA expression was altered by low and medium dose exposure sourced predominantly from genes influencing the p53 pathway. CircRNAs and transcribed from the () tumor suppressor (a p53 regulator) responded within hours to IR. and were present in exosomes yet exhibited differential transcript clearance between irradiated cell lines. Dual-quasar labelled probes and hybridization demonstrated the intercellular distribution of and predominantly within the perinucleus. QKI knockdown removed nuclear expression of these circRNAs with no significant effect on cytosolic and Distinct QKI transcription between cell lines and its augmented interaction with and was noted post IR. This foremost study provides evidence that QKI and circRNAs partake in the cellular irradiation response. and as stable secreted circRNAs may afford vital characteristics worth syphoning as promising diagnostic radiotherapy biomarkers.
环状RNA(circRNAs)由震颤蛋白(QKI)生成,是新发现的非编码RNA(ncRNA)成员,具有组织特异性、稳定性增强以及在外泌体中富集的特点。研究表明,电离辐射(IR)可影响ncRNA转录。然而,尚不清楚circRNAs或QKI是否受IR调控。微阵列circRNA分析和下一代测序显示,低剂量和中等剂量照射会改变circRNA表达,这些照射主要来自影响p53通路的基因。从肿瘤抑制基因(一种p53调节因子)转录而来的circRNAs在数小时内对IR产生反应。和存在于外泌体中,但在受照射细胞系之间表现出不同的转录物清除情况。双量子点标记探针和杂交显示和主要在细胞核周围的细胞间分布。QKI敲低消除了这些circRNAs的核表达,对细胞质中的和没有显著影响。在IR后,细胞系之间存在明显的QKI转录,并且其与和的相互作用增强。这项首要研究提供了证据,表明QKI和circRNAs参与细胞辐射反应。和作为稳定分泌的circRNAs可能具有重要特征,值得作为有前景的诊断性放射治疗生物标志物加以利用。