GABRDpromotes the progression of breast cancer through CDK1-dependent cell cycle regulation

Abstract

AbstractPurposeY-aminobutyric acid (GABA) is an important inhibitory amino acid neurotransmitter that exerts its biological function by binding to GABA receptors, which not only play an important role in neuromodulation, but also involved in regulating the development of tumors. Gamma-aminobutyric acid type A receptor subunit delta (GABRD) encodes the δ subunit of GABAAreceptor, its impact on breast cancer has not been clearly studied. This study is aiming to reveal the relationship betweenGABRDand breast cancer development.MethodsWe performed a tissue microarray to quantifyGABRDexpression levels in tumor tissue and paracarcinoma tissue. The regulation ofGABRDin the proliferation, migration, and apoptosis of breast cancer was examined by a loss-of-function study. A GeneChip microarray was used to probe GABRD for potential downstream molecules. The interaction between GABRD and CDK1 was verified by a set of functional tests and rescue experiments as well as coimmunoprecipitation.ResultsGABRDwas expressed at significantly higher levels in tumor tissues and was associated with advanced tumor progression. SilencingGABRDresulted in a significant decrease in proliferation and migration and an increase in apoptosis of breast cancer.GABRDregulated the cell cycle by directly interacting with CDK1, which was identified as an important downstream target.ConclusionGABRDis the breast cancer-related gene and highlights the importance of the GABRD–CDK1 axis in regulating breast cancer proliferation, which provides potential for the development of novel therapeutics.