长链非编码RNA OIP5-AS1通过调控miR-424靶向IDH3α影响肺腺癌糖酵解 的机制及分子影像学研究

Tumor cells still obtain energy through glycolysis pathway even in the aerobic environment is known as aerobic glycolysis. Targeting tumor glycolysis is a novel approach to tumor therapy. Our previous studies found that the expression of IDH3α which is a rate-limiting enzyme of tricarboxylic acid cycle is closely related to glycolysis and IDH3α through AKT-Glut1 pathway impacts glycolysis in lung adenocarcinoma. However, little is known about the upstream mechanism of glycolysis regulated by IDH3α. The research of regulatory mechanism targeted genes by the interaction of LncRNA and microRNA is an emerging hotspot in recent years. There are targeted relationships between miR-424 and IDH3α, LncRNA OIP5-AS1 and miR-424. One of the objectives of this study is to evaluate that LncRNA OIP5-AS1 through miR-424 by targeting IDH3α impacts glycolysis in lung adenocarcinoma by overexpression and knockdown of LncRNA OIP5-AS1 and miR-424 at the cellular level. In addition, the animal models will be established to verify the regulatory mechanism in vivo by the 18F-FDG Micro-PET imaging. In summary, our studies aim to provide experimental evidences for targeting tumor glycolysis.

肿瘤细胞在有氧环境下，仍通过糖酵解提供能量，称为有氧糖酵解。靶向肿瘤糖酵解是肿瘤治疗的新途径。课题组前期研究发现，三羧酸循环限速酶IDH3α的表达与肺腺癌糖酵解密切相关，IDH3α通过AKT-Glut1路径影响糖酵解。但IDH3α调控肺腺癌糖酵解的上游机制尚不清楚。长链非编码RNA（LncRNA）和微小RNA（microRNA）相互作用调控靶基因正成为研究的热点。miR-424与IDH3α、LncRNA OIP5-AS1与miR-424具有靶向结合位点，但它们之间的相互作用对肺腺癌糖酵解的影响亟待探明。本项目组拟通过上调和下调LncRNA OIP5-AS1与miR-424的表达，在细胞水平观察LncRNA OIP5-AS1通过调控miR-424靶向IDH3α对肺腺癌糖酵解的影响；构建动物模型，应用18F-FDG Micro-PET显像在体验证调控机制。为靶向肿瘤糖酵解的治疗提供依据。

肿瘤细胞在有氧环境下，仍通过糖酵解提供能量，称为有氧糖酵解。靶向肿瘤糖酵解是肿瘤治疗的新途径。长链非编码RNA（LncRNA）和微小RNA（microRNA）相互作用调控靶基因正成为研究的热点。课题组以LncRNA- microRNA-靶基因为依托，通过不同程度的临床研究、细胞实验和动物实验的开展，深入探讨和明确相关基因与肺腺癌糖酵解的相关性。在组织层面明确相关基因在肺腺癌中的临床意义，在细胞层面明确相关基因在肺腺癌细胞系中的调控糖酵解具体分子机制，在动物水平进行肿瘤模型的分子影像动态评价和在体相关分子机制验证。课题组以探讨相关基因与肺腺癌糖酵解的相关性为出发，旨在发掘抗肿瘤能量代谢治疗的潜在靶点，最终为肺腺癌的诊断和治疗提供有力依据。