miR-33a抑制糖酵解途径影响黑色素瘤放射敏感性的实验研究

放射治疗为黑色素瘤重要的治疗手段之一，如何提高黑色素瘤的放射敏感性是目前亟待解决的难题。我们前期发现黑色素瘤细胞中miR-33a低表达；HIF-1α为miR-33a的直接靶基因；miR-33a明显抑制肿瘤细胞的有氧糖酵解和增殖。结合MicroRNA、HIF-1α及糖酵解均能影响肿瘤的放射敏感性，本课题以黑色素瘤细胞中miR-33a能够抑制糖酵解途径而影响肿瘤细胞放射敏感性为主轴，首先深入验证miR-33a通过调控HIF-1α等抑制糖酵解途径；再利用体内外模型观察miR-33a对黑色素瘤细胞放射敏感性的影响，并探讨miR-33a通过抑制糖酵解途径影响黑色素瘤细胞放射敏感性的分子机制；最后利用现有临床资料和标本，判定miR-33a及糖酵解表型在黑色素瘤放射治疗预后评估、复发预测中的临床价值。以求寻找黑色素瘤放射治疗新靶点，为临床上黑色素瘤的放射治疗增敏及放射治疗个体化方案提供科学依据。

Radiotherapy is one of the important treatments for melanoma, and radiosensitivity is a major obstacle in clinical treatment. Our preliminary experiments revealed that miR-33a was down-regulated in melanoma cells, HIF-1α was the direct target gene of miR-33a and miR-33a significantly inhibited aerobic glycolysis and proliferation in melanoma cells. Since MicroRNA, HIF-1α and glycolysis could affect the radiosensitivity of tumor cells, we focus on the idea that miR-33a could affect the radiosensitivity of melanoma cells by inhibiting the glycolytic pathway. Our study will further confirm miR-33a inhibit the glycolysis by regulating HIF-1α and other genes, then observe the impact of miR-33a on the radiosensitivity of melanoma cells by in vitro and in vivo models. In addition, we will investigate the molecular mechanism of miR-33a affecting the radiosensitivity of melanoma cells by inhibiting glycolysis. Moreover,by using existing clinical samples, we will validate the clinical values of miR-33a and glycolytic phenotype for the prognostic assessment and recurrent prediction of melanoma patients received radiotherapy. Our study will try to identify novel targets for radiosensitivity of melanoma, which would provide scientific evidence for melanoma radiosensitivity enhancing and individualized radiotherapeutic regimen.