MicroRNA-140-5p suppresses invasion and proliferation of glioma cells by targeting glutamate-ammonia ligase (GLUL)

Ru Zhang, Jin-Chao Zhu, Hai Hu, Qin-Yuan Lin,  Wei Shao,  Tian-Hai Ji

Abstract:

Glutamine addiction is a major feature of glioma cells and plays an important role in its growth and proliferation. GLUL (glutamate-ammonia ligase), which catalyzes glutamate and ammonia to synthesize glutamine, plays a crucial role in tumor growth and proliferation. We attempt to determine a pathway that limits the growth of glioma by targeting GLUL and explore effective strategies blocking glutamine metabolism. We note that miRNAs mediate regulation of genes participating directly or indirectly in cancer cell metabolism. The regulatory roles of miRNAs on metabolic enzymes are widely discussed, however miRNAs regulation of glutamine metabolism by targeting GLUL in glioma has not yet been reported. Here, we examined both the expression and functions of GLUL in glioma cells. Findings indicated that the expression of GLUL was upregulated in high-grade compared to low-grade glioma cells. Knockdown of GLUL effectively inhibited proliferation, migration and invasion of glioma cells in vitro. Bioinformatics analyses, as well as dual-luciferase reporter assays, revealed that miR-140-5p bound to GLUL mRNA at the 3’-UTR location. Furthermore, the proliferation, migration and invasion of glioma cells were also repressed by miR-140-5p. Overall, these results showed that miR-140-5p exerted its inhibitory effects on proliferation, migration and invasion in glioma cells through downregulating GLUL. Thus, the miR-140-5p/GLUL axis may function as a potential target for glioma treatment.