CAPRIN1结合LINC00493促进磷酸戊糖途径影响胶质瘤生物学行为的分子机制

Glioma is a kind of solid tumor with high metabolism. High metabolic level is an important factor in promoting its rapid growth. Previous studies showed that CAPRIN1 was upregulated in glioma tissue and glioma cell lines (GCs). Down regulation of CAPRIN1 could significantly inhibit the expression of G6PD, a key limiting enzyme in pentose phosphate pathway (PPP), and affect the PPP process, GCs proliferation, migration and invasion. In GCs, the expression of LINC00493 was up-regulated, miR-448 was down-regulated, and MEF2C was up-regulated. Through a series of previous studies, we speculated that CAPRIN1 may combine and promote the expression of LINC00493, which will weaken the negative regulation role of miR-448 on MEF2C. MEF2C can bind to the promoter region of G6PD and promote its expression, thereby promoting the PPP process and biological behavior of glioma. This project can not only clarify the molecular mechanism of CAPRIN1 combined with LINC00493 to the promote pentose phosphate pathway and biological behavior of glioma, but can also provide new targets and theoretical basis for the metabolic therapy of glioma.

胶质瘤是一种代谢旺盛的实体性肿瘤，高代谢水平是促进其快速生长的重要因素。前期研究发现，CAPRIN1在胶质瘤组织及胶质瘤细胞(GCs)中表达上调，下调CAPRIN1能够显著抑制磷酸戊糖途径(PPP)关键限速酶G6PD的表达，影响PPP过程及GCs增殖、迁移和侵袭能力。GCs中LINC00493表达上调，miR-448表达下调，MEF2C表达上调。通过系列前期研究推测，CAPRIN1可能结合并促进了LINC00493的表达，减弱了miR-448对MEF2C的负性调控作用，MEF2C能够与G6PD的启动子区结合并促进其表达，进而促进了PPP过程及胶质瘤生物学行为。本项目不仅能明确CAPRIN1结合LINC00493促进磷酸戊糖途径及胶质瘤生物学行为的分子机制，而且能够为胶质瘤的代谢治疗提供新的靶点和理论依据。

胶质瘤是一种代谢旺盛的实体性肿瘤，高代谢水平是促进其快速生长的重要因素，如何抑制胶质瘤快速生长一直是临床治疗的难点。本研究首先明确CAPRIN1，LINC01641，GBX1及G6PD在胶质瘤组织及细胞系中的表达水平，验证CAPRIN1与LINC01641，LINC01641与GBX1，以及GBX1与G6PD间的结合作用，并明确结合位点。进一步通过研究胶质瘤细胞中CAPRIN1、LINC01641、GBX1表达变化对磷酸戊糖途径及胶质瘤细胞恶性生物学行为的影响。通过研究发现，CAPRIN1、LINC01641和G6PD在胶质瘤组织和细胞中高表达，GBX1低表达。胶质瘤细胞中下调CAPRIN1能够通过调控LINC01641靶向调节GBX1，进而调控磷酸戊糖途径(PPP)关键限速酶G6PD的表达，影响PPP过程及GCs增殖、迁移和侵袭能力。本项目不仅能明确CAPRIN1结合LINC01641促进磷酸戊糖途径及胶质瘤生物学行为的分子机制，而且能够为胶质瘤的代谢治疗提供新的靶点和理论依据。