miR-300与肿瘤放疗耐受性的研究

肿瘤是严重威胁人类健康的主要疾病之一，其发病率呈现逐年上升的趋势。放射治疗是恶性肿瘤治疗的常规手段，但由于肿瘤细胞的放射耐受性使得放疗往往无法达到预期效果。microRNA是一类内源性非编码小RNA分子，在肿瘤发生发展的各阶段发挥重要调控功能，如增殖、凋亡、侵袭和迁移、血管生成等。目前，越来越多证据表明miRNA与肿瘤放化疗耐受密切相关。我们前期研究发现miR-300能够促进肿瘤细胞电离辐射诱导的DNA损伤修复及G2细胞周期阻滞，miR-300可能是通过调控TP53/APAF1凋亡通路而发挥放疗耐受的功能。本课题拟通过多种生物学终点检测miR-300对肿瘤细胞及小鼠异种移植瘤放疗耐受性的影响，在体外、体内深入探索miR-300的放疗耐受功能及其对TP53/APAF1的靶向负调控，旨在阐明miR-300发挥放化疗耐受功能的机制，为miRNA辅助肿瘤放疗在临床上的应用提供可靠的理论及实验依据。

Tumor is one of the most common health diseases worldwide, which incidence is increasing year by year. Radiotherapy, one common form of cancer treatments, always cannot attain the maximal efficacy because of radioresistance of tumor cells. microRNA is a kind of endogenous small non-coding RNA, involving in regulating almost all aspects of tumor biology, such as proliferation, apoptosis, invasion and metastasis, angiogenesis and so on. Furthermore, more and more evidence indicated that miRNA is implicated in tumor radioresistance and chemoresistance. Our recent study found that miR-300 plays an important role in regulating radioresistance of tumor cells by enhancing the cellular DNA damage repair ability and rescuing DNA damage induced G2 cell cycle arrest through mediating the TP53/APAF1 pathway. In the present study, we set up a series of experiments to validate TP53/APAF1 are the direct targets of miR-300 and identify the effect of miR-300 on radioresistance in vitro and in vivo. The aim of the present study is attempting to elucidate the mechanism of which miR-300 function in radioresistance and provide reliable theory and experiment proof for the clinical application of miR-300.