NFATc3转录调控MMP14介导少突胶质细胞瘤血管新生促肿瘤恶变的机制研究

少突胶质细胞瘤(OG)是中青年常见的原发性低级别脑胶质瘤。我们前期研究发现血管新生促进的OG肿瘤恶变是病人复发和死亡的重要原因，但具体机制尚不清楚。本项目通过临床数据的筛选发现OG病人的肿瘤恶变伴随着NFATc3和MMP14的表达升高以及血管新生增加；在细胞及分子水平层面进一步发现NFATc3转录调控MMP14从而介导肿瘤血管新生。据此，我们提出NFATc3通过转录调控MMP14影响血管新生，并在OG肿瘤恶变的发生发展中起关键作用。本项目拟揭示NFATc3、MMP14和血管新生在OG肿瘤恶变临床上的相关性，阐明NFATc3调节MMP14的分子机制和血管新生的信号通路。此外，本项目将利用腺病毒敲低NFATc3和MMP14以及多肽库筛选相关抗肿瘤药物，并在体内和体外验证其在OG肿瘤恶变中的临床应用价值。本研究有望揭示影响OG肿瘤恶变的新机制，为临床治疗提供理论基础和新靶点依据。

Oligodendrogliomas (OG) is a primary low-grade glioma in young and middle-aged people. Our previous publication showed that the malignancy induced by angiogenesis in OG is one of the mainly causes of recurrence and death in clinic, but the mechanism is still unclear. Firstly, our previous study analyzed the data from clinical data and found that the expression of NFATc3, MMP14 and angiogenesis is positive related with the level of malignancy in OG. Furthermore, we observed that NFATc3 regulated MMP14 transcription and angiogenesis then lead OG malignancy in vitro. Thus, our hypothesis is that NFATc3 regulated MMP14 transcription and angiogenesis and play a key role in the occurrence and development of malignant transformation of OG. This project intends to study the correlation between NFATc3, MMP14 and angiogenesis in malignant transformation of OG, and to elucidate the molecular mechanism of NFATc3 transcriptional regulation of MMP14 and the signal pathway of angiogenesis. In addition, this project will use the Adenovirus knockdown and peptide library to screen anticancer drugs that inhibit the expression of NFATc3 and MMP14 and verify their clinical application value in malignant transformation of OG in vivo and in vitro. It is expected to reverse OG malignancy, clarify the mechanism of NFATc3 and MMP14 on tumor malignancy, which may be potentially the new targets for clinical treatment of OG.