Modulation of microRNAs by ionizing radiation in human gastric cancer
Modulation of microRNAs by ionizing radiation in human gastric cancer
复制标题
人胃癌中电离辐射对 microRNA 的调节。
DOI：
10.3892/or.2014.3246
复制
发表时间：
2014-08-05
期刊：
影响因子：
4.2
通讯作者：
Wang, Jufang
中科院分区：
文献类型：
--
作者：
He, Jinpeng;Hua, Junrui;Wang, Jufang
胃癌是我国最常见的恶性肿瘤之一。虽然手术是主要的治疗方法，但放射治疗已成为不可或缺的一部分，特别是在胃癌的早期和中期。microRNA（miRNAs）参与调节响应于内在和外在应激的多种细胞过程。已经在各种类型的肿瘤细胞中鉴定了对辐射响应的miRNA表达谱的变化;然而，没有关于胃癌的相关信息。在本研究中，我们使用miRNA微阵列研究了暴露于X射线的两个临床胃癌样本的miRNA谱。我们发现，与未照射的样品相比，16个miRNAs下调，2个miRNAs显著上调。在更多的临床样本和培养的细胞系中，通过qRT-PCR证实了miR-300和miR-642表达水平的降低。利用TargetScan软件对两种miRNAs的靶点进行了预测，并利用Gene Ontology软件对候选靶点进行了分类，结果表明miR-300和miR-642均可能通过调节细胞凋亡、细胞周期调控以及DNA损伤修复通路相关基因来调控细胞辐射反应。细胞周期分析和免疫荧光分析表明，miR-300调节辐射诱导的G2期细胞阻滞和DNA损伤修复。总之，我们的研究结果表明电离辐射调节了miRNA的表达谱，并且miR-300等几种特定miRNA的变化有可能用于胃癌的治疗、诊断和预后。
Gastric cancer is one of the most common cancers in China. Although surgery is the primary therapeutic method, radiotherapy has become an integral part, particularly in the early and intermediate stages of gastric cancer. microRNAs (miRNAs) are involved in the regulation of diverse cellular processes in response to intrinsic and extrinsic stress. A change in miRNA expression profile has been identified in various types of tumor cells in response to radiation; however, there is no relevant information concerning gastric cancer. In the present study, we investigated the miRNA profiles of two clinical gastric cancer samples exposed to X‑rays using miRNA microarray. We found that 16 miRNAs were downregulated and 2 miRNAs were upregulated significantly in both irradiated samples when compared with the unirradiated samples. Decreases in the levels of miR‑300 and miR‑642 expression were confirmed by qRT‑PCR in more clinical samples and in cultured cell lines. We predicted the targets of the two miRNAs with TargetScan and classified all the candidate targets with Gene Ontology, which indicated that both miR‑300 and miR‑642 potentially regulate cellular radiation response by modulating apoptosis, cell cycle regulation and DNA damage and repair pathway-related genes. Cell cycle assay and immunofluorescence assay demonstrated that miR‑300 regulates radiation‑induced G2 cell cycle arrest and DNA damage repair. In conclusion, our findings indicate that ionizing radiation modulates the miRNA expression profile, and the changes in several specific miRNAs such as miR‑300 have the potential to be used in the treatment, diagnosis and prognosis of gastric cancer.