He Jinpeng, Hua Junrui, Ding Nan, Xu Shuai, Sun Rui, Zhou Guangming, Xie Xiaodong, Wang Jufang
Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 73000, P.R. China.
Department of Oncology, The First People's Hospital of Lanzhou, Lanzhou 730000, P.R. China.
Oncol Rep. 2014 Aug;32(2):787-93. doi: 10.3892/or.2014.3246. Epub 2014 Jun 11.
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.
胃癌是中国最常见的癌症之一。尽管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，尤其是在胃癌的早期和中期。微小RNA（miRNA）参与响应内在和外在应激时多种细胞过程的调控。在各种类型的肿瘤细胞中，已发现miRNA表达谱会因辐射而发生变化；然而，关于胃癌的相关信息却尚无报道。在本研究中，我们使用miRNA微阵列研究了两个接受X射线照射的临床胃癌样本的miRNA谱。我们发现，与未照射样本相比，两个照射样本中均有16种miRNA显著下调，2种miRNA显著上调。通过qRT-PCR在更多临床样本和培养细胞系中证实了miR-300和miR-642表达水平的降低。我们使用TargetScan预测了这两种miRNA的靶标，并通过基因本体论对所有候选靶标进行了分类，这表明miR-300和miR-642均可能通过调节凋亡、细胞周期调控以及与DNA损伤和修复途径相关的基因来调控细胞的辐射反应。细胞周期分析和免疫荧光分析表明，miR-300可调节辐射诱导的G2期细胞周期阻滞和DNA损伤修复。总之，我们的研究结果表明，电离辐射可调节miRNA表达谱，并且几种特定miRNA（如miR-300）的变化有可能用于胃癌的治疗、诊断和预后评估。
