Study On MicroRNA And Tumor Cell Radiosensitivity

Tumor, especially the malignant tumor, is one of the serious diseases threaten human health and life, which morbidity and mortality are continuously increasing year by year. Now, it has ranked the leading cause of human deaths worldwide. Radiotherapy is widely used in clinical tumor treatment for its remarkable effect and clear adverse reactions. It is well known that the tumor radiosensitivity is the main factor impairing the radiotherapy effect, how to decrease the radioresistance of tumor cells and protect the normal tissues from radiation damage as more as possible are the challenge for clinical researchers, so it is very important to study the mechanism of tumor radiosensitivity for further understanding the radioresistance of tumor cells and the development of novel radiosensitizer. Although the radiobiology has made rapid progress in recent years, the molecular mechanism of tumor cell radiosensitivity remain largely undetermined.micro RNAs(mi RNAs) are one novel class of endogenous small non-coding RNAs which regulate gene expression by affecting both the stability and translation of m RNAs through base pairing with the target m RNA at post-transcriptional level. It has been reported that in human genome the expression of more than 60% genes are regulated by mi RNAs, and they can regulate nearly all progresses in cells, such as cellular proliferation, differentiation, death and so on. Recently, more and more evidence showed mi RNAs are involved in the regulation of tumor radiosensitivity, which maybe new potential clinical target for radiation sensitization.In recent study, we detected the mi RNA profile of clinical cancer tissue samples exposed to 4Gy of X-rays by using mi RNA microarray and found that mi R-185 and mi R-300 were dramatically downregulated in kidney and gastric cancer after irradiation respectively. To explore the relationship between mi RNA and tumor radiosensitivity, meanwhile, to illustrate the molecular mechanism how mi RNA regulates tumor cells resistance to ionizing radiation(IR), in the present study, we tested the effects of mi R-185 and mi R-300 on the colony formation, transplantation tumor, DNA damage repair, cell cycle arrest and apoptosis in kidney and gastric cancer cells. Our results showed that mi R-185 decreased the colony formation ability and tumorigenic ability of 786-O cells irradiated to IR in vitro and in vivo. Moreover, we demonstrated that mi R-185 significantly promoted apoptosis and proliferation inhibition induced by IR through targeting ATR, which is one of the most important sensors and transducers in DNA damage response signal pathway. In addition, we found out that mi R-300 enhanced the radioresistance of tumor cells to IR through regulation of cellular DNA damage repair and cell cycle arrest induce by IR.