Abstract
Glutamate ionotropic receptor kainate type subunit 3 (GRIK3) is a predominant excitatory neurotransmitter receptor in the mammalian brain. While it is known that GRIK3 is involved in normal neurophysiologic processes, its biological functions in tumor progression are still poorly understood due to limited investigation. In this study, we reported for the first time that GRIK3 expression was downregulated in non-small cell lung cancer (NSCLC) tissues as compared to paracarcinoma tissues. Additionally, we observed that GRIK3 expression was strongly correlated with the prognosis of NSCLC patients. We also noted that GRIK3 suppressed the cell proliferation and migration capability of NSCLC cells, thereby inhibiting xenografts growth and metastasis. Mechanistically, GRIK3 deficiency increased the expression of ubiquitin-conjugating enzyme E2 C (UBE2C) and cyclin-dependent kinase 1 (CDK1), which resulted in the activation of the Wnt signaling pathway and enhanced NSCLC progression. Our findings suggest that GRIK3 plays a role in regulating NSCLC progression and that its expression may serve as an independent prognostic indicator for NSCLC patients.