神经胶质瘤是最常见,最具侵袭性的原发性脑肿瘤。目前对胶质瘤治疗的效果不佳，缺乏特异、有效的分子标志物对其分型和预后进行准确的诊断与评估。HOTAIRM1作为粒细胞中特异表达的长链非编码RNA，在不同的胶质瘤样本数据库中都显示较正常脑组织中的表达显著上调，但并不知道它在胶质瘤中的具体功能和作用机制。我实验室在前期研究中发现它在经典和间质亚型的胶质瘤中高表达，并且与患者的预后呈负相关。敲低其表达可有效抑制胶质瘤细胞体外和体内的增殖能力，并且显著抑制细胞线粒体功能。我们还通过基因表达谱芯片，发现HOTAIRM1可以调节线粒体中的丝氨酸分解酶SHMT2的表达。本项目旨在进一步探索HOTAIRM1对胶质瘤线粒体功能的影响和对SHMT2的分子调节机制。该工作将揭示长链非编码RNA在神经胶质瘤中的新功能和新机制。

Glioma is the most common and the most aggressive primary brain tumor. Up until recently, the effect of clinical treatment on glioma has a poor prognosis. The more specific and effective molecular markers remain still lacked for accurate subtype diagnosis and prognosis evaluation of glioma. HOTAIRM1, a myeloid-specific long non-coding RNA, was significantly up-regulated compared with normal brain tissues in the glioma samples from different databases. But we still don't know its precise function and mechanism in gliomas. Our previous studies showed that its expression was obviously increased in classical and mesenchyma subtypes of glioma tissues, and negatively correlated with the prognosis of the patients. Knockdown of its expression could effectively inhibit the glioma cell proliferation capacity in vitro and in vivo, and particularly weaken the function of cellular mitochondrial respiratory. Through the analysis of gene expression profile microarray, we also found that HOTAIRM1 would regulate the expression of the mitochondrial serine catabolic enzyme, SHMT2 (serine hydroxymethyltransferase 2). Based on the previous work, this project will furtherly study the effect of HOTAIRM1 on mitochondrial function of glioma cells and the molecular mechanism in the regulation of SHMT2. This work will reveal the novel feature and mechanism of a long non-coding RNA in glioma.