Department of Radiation Oncology, Ludwig-Maximilians University of Munich, Germany.
Radiat Oncol. 2011 Mar 31;6:29. doi: 10.1186/1748-717X-6-29.
MicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. MicroRNAs also modulate responses to anti-cancer therapy. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. However, changes in microRNA expression profiles in response to irradiation have not been comprehensively analyzed so far. The present study's intend is to present a broad screen of changes in microRNA expression following irradiation of different malignant cell lines.
1100 microRNAs (Sanger miRBase release version 14.0) were analyzed in six malignant cell lines following irradiation with clinically relevant doses of 2.0 Gy. MicroRNA levels 6 hours after irradiation were compared to microRNA levels in non-irradiated cells using the "Geniom Biochip MPEA homo sapiens".
Hierarchical clustering analysis revealed a pattern, which significantly (p = 0.014) discerned irradiated from non-irradiated cells. The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation. Moreover, several microRNAs previously not known to be radiation-responsive were discovered.
Ionizing radiation induced significant changes in microRNA expression profiles in 3 glioma and 3 squamous cell carcinoma cell lines. The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis.
microRNAs 是细胞内过程的重要调节因子,与人类癌症的发病机制和预后有关。microRNAs 还调节抗肿瘤治疗的反应。在放射肿瘤学领域,发现 microRNAs 在照射后调节细胞死亡和增殖。然而,迄今为止,还没有全面分析 microRNA 表达谱对照射的反应。本研究旨在广泛筛选不同恶性细胞系照射后 microRNA 表达的变化。
在 6 种恶性细胞系中,用临床相关剂量 2.0 Gy 照射后,分析了 1100 个 microRNAs(桑格 miRBase 发布版本 14.0)。用“Geniom Biochip MPEA homo sapiens”比较照射后 6 小时的 microRNA 水平与未照射细胞的 microRNA 水平。
层次聚类分析显示,一种模式能显著(p = 0.014)区分照射细胞和未照射细胞。一些已知参与细胞过程调节的 microRNAs(如凋亡、增殖、侵袭、局部免疫反应和放射抵抗)的表达水平在照射后发生了 2-3 倍的变化(如 miR-1285、miR-24-1、miR-151-5p、let-7i)。此外,还发现了一些以前不知道对辐射有反应的 microRNAs。
电离辐射诱导 3 个神经胶质瘤和 3 个鳞状细胞癌细胞系的 microRNA 表达谱发生显著变化。这些变化的功能相关性尚未得到解决,但应通过未来的工作进行分析,特别是特别关注临床相关终点,如辐射诱导的细胞死亡、增殖、迁移和转移。