Modulation of microRNAs by ionizing radiation in human gastric cancer

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 Target Scan 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.