Promotion of lung cancer growth via glutamate ionotropic receptor N-methyl-D-aspartate-type subunit 2D (<i>GRIN2D</i>).

Abstract

<h4>Background</h4>N-methyl-D-aspartate receptors (NMDARs) are known to contribute to neurological and neurodegenerative diseases. Meanwhile, glutamate ionotropic receptor N-methyl-D-aspartate-type subunit 2D (<i>GRIN2D</i>), which encodes NMDAR subunit 2D, may play a role in colorectal cancer. The study examined whether <i>GRIN2D</i> is involved in lung cancer.<h4>Methods</h4>Through the use of quantitative reverse-transcription polymerase chain reaction (qRT-PCR), <i>GRIN2D</i> expression was detected in tissue samples and cell lines. EdU staining assay was used to determine the cell proliferation ability, while TUNEL staining assay was used to evaluate apoptosis. The phosphorylation levels of PI3K, AKT, and mTOR were measured via Western blotting; cell viability was evaluated via Cell Counting Kit-8 (CCK-8) assay; and colony formation ability was examined via colony formation assay.<h4>Results</h4>In this study, we demonstrated that lung adenocarcinoma and related cancer cell lines had significantly high levels of <i>GRIN2D</i> expression. <i>GRIN2D</i> promoted cancer cell proliferation while inhibiting apoptosis via the PI3K/mTOR signaling pathway. Esketamine, a <i>GRIN2D</i> inhibitor, and LY294002, a PI3K inhibitor, either alone or in combination, could suppress the tumor growth induced by high <i>GRIN2D</i> levels both <i>in vitro</i> and <i>in vivo</i>.<h4>Conclusions</h4>This study is the first to identify the involvement of <i>GRIN2D</i> in lung cancer and to clarify the underlying mechanism of its effect; the findings further suggest that ketamine in cancer treatment may extend beyond relieving pain and depression.

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