β-肾上腺素能受体上调MALAT1促进脑胶质瘤发生的机制研究

脑胶质瘤是增殖、迁移侵袭能力极强的恶性脑瘤，占颅内肿瘤的50%以上。研究发现，β-肾上腺素能受体（β-AR）与肿瘤的发生发展密切相关，但它在脑胶质瘤中的作用及分子机制仍有待进一步研究。本课题前期实验结果显示，脑胶质瘤细胞高表达β-AR，并且首次发现激活β-AR后可上调长链非编码RNA MALAT1，进而促进脑胶质瘤细胞增殖。基于上述结果，本项目将在细胞水平和体内动物模型上揭示β-AR在促进脑胶质瘤发生过程中的精细分子机制，深入研究：1）β-AR上调MALAT1过程中的相关信号机制；2）明确β-AR各亚型对脑胶质瘤增殖的作用；3）体内动物模型验证β-AR在脑胶质瘤发生中的作用。本研究有助于为脑胶质瘤的治疗提供新的理论基础。

Glioblastoma is one of the strongest human malignant tumor with high ability of migration and invasion, which accounts for above 50% of all brain cancer. Recent studies revealed that β-adrenergic receptor (β-AR) is closely related to the occurrence and development of cancer, but the function and molecular mechanism of β-AR in glioblastoma needs to be further studied. Our previous results indicated that β-AR was high expressed in glioblastoma cells. Activation of β-AR could significantly promote proliferation of glioblastoma cells through upregulating the expression of long non-coding RNA MALAT1. Based on these results, we will further investigate the functional mechanism of β-AR in promoting glioblastoma cell growth both at the cellular level and in vivo animal xenograft models, and intend to study: 1) the molecular mechanism underlying β-AR-mediated upregulation of MALAT1; 2) the role of different subtypes of β-AR in the proliferation of glioblastoma; 3) the role of β-AR in glioblastoma development in vivo animal xenograft models. This study will provide a new theoretical basis for the glioblastoma treatment.