GRIN2D knockdown suppresses the progression of lung adenocarcinoma by regulating the E2F signalling pathway

Zhitao Chen; Yanhui Song; Peipei Li; Wei Gao

doi:10.1016/j.cellsig.2023.110685

GRIN2D knockdown suppresses the progression of lung adenocarcinoma by regulating the E2F signalling pathway

Cell Signal. 2023 Jul:107:110685. doi: 10.1016/j.cellsig.2023.110685. Epub 2023 Apr 19.

Authors

Zhitao Chen¹, Yanhui Song², Peipei Li³, Wei Gao⁴

Affiliations

¹ Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China.
² Department of Internal Medicine, Rongfu Military Hospital of Jining City, Jining 272101, Shandong, China.
³ Department of General Surgery, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China.
⁴ Department of Pathology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China. Electronic address: gw98755@163.com.

PMID: 37084840
DOI: 10.1016/j.cellsig.2023.110685

Abstract

Objective: Glutamate ionotropic receptor N-methyl-d-aspartate (NMDA) type subunit 2D (GRIN2D) is a member of the GRIN gene family and contributes to the development and function of the brain. GRIN2D was found to be upregulated in several types of cancers; however, its mechanism in lung adenocarcinoma (LUAD) remains unclear.

Methods: We determined the role of GRIN2D in LUAD. In addition, we investigated the potential mechanism of GRIN2D in LUAD using bioinformatics analysis and confirmed this mechanism using biological approaches.

Results: GRIN2D was found to be upregulated in LUAD tissues and cells. GRIN2D knockdown reduced the proliferation and accelerated the apoptosis of LUAD cells. GRIN2D also activated glycolysis, gluconeogenesis, and the E2F signalling pathway in LUAD. GRIN2D knockdown significantly inhibited glucose uptake, lactate production, the ATP/ADP ratio, ECAR, and OCR in LUAD cells. E2F1 overexpression eliminated the inhibitory effect of GRIN2D knockdown in LUAD cells.

Conclusions: GRIN2D knockdown suppresses cell growth, migration, glycolysis, and gluconeogenesis of LUAD by inhibiting the E2F signalling pathway.

Keywords: E2F signalling pathway; GRIN2D; Glycolysis; Lung adenocarcinoma.

MeSH terms

Adenocarcinoma of Lung* / genetics
Adenocarcinoma*
Cell Proliferation / genetics
Gene Expression Regulation, Neoplastic
Humans
Lactic Acid
Lung Neoplasms* / genetics
Receptors, N-Methyl-D-Aspartate
Signal Transduction

Substances

Lactic Acid
GRIN2D protein, human
Receptors, N-Methyl-D-Aspartate