The Functional Interplay among GAD2, GABRG2, and CACNA1G Genes in Cancers

Indrasari, Sagung Rai; Darmayanti, Salma; Zafrullah, Adila; Lessy, Nina Sakina; Haryana, Sofia Mubarika; Sadewa, Ahmad Hamim; Oktriani, Risky

doi:10.31557/APJCP.2025.26.8.2709

The Functional Interplay among GAD2, GABRG2, and CACNA1G Genes in Cancers

Document Type : Systematic Review and Meta-analysis

Authors

¹ Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

² Master’s Program in Biomedical Sciences, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

³ Collaboration Research Center for Precision Oncology based Omics (PKR PrOmics), Yogyakarta, Indonesia.

⁴ Department of Histology and Cell Biology, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

⁵ Department of Biochemistry, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

10.31557/APJCP.2025.26.8.2709

Abstract

The GABAergic system, commonly known as the inhibitory system in the central nervous system, also plays a crucial role in cancer development. Objective: This article reviews the complex interactions between the GABAergic system and tumor progression, emphasizing the GAD2, GABRG2, and CACNA1G genes. Method: A comprehensive literature review was conducted to assess current evidence regarding the involvement of GAD2, GABRG2, and CACNA1G genes in promoting cancer development through enhanced tumor growth, cell survival, and increased intracellular calcium levels. Result: While GABA generally suppresses neural activity, it can paradoxically promote cell proliferation and survival in cancer cells. The GAD2 gene produces an enzyme that helps create GABA. Higher levels of GAD2 expression have been linked to tumor growth and survival in several types of cancer. The GABRG2 gene encodes a subunit of the GABA-A receptor. When this receptor is activated, it can cause depolarization and activate signaling pathways that promote cancer cell growth. The CACNA1G gene encodes a subunit of a calcium channel that controls calcium ion entry into cells. Higher levels of CACNA1G expression are frequently found in various cancers, contributing to tumor development by increasing intracellular calcium levels. Conclusion: This article examines the role of GAD2, GABRG2, and CACNA1G genes in cancer progression, highlighting their interactions in promoting tumor growth and survival. A deeper understanding of the molecular mechanisms underlying GABA signaling, its receptors, and the associated genes in cancer could lead to the identification of new therapeutic targets and the development of more effective treatments. Further research is essential to elucidate the detailed mechanisms driving cancer development and progression.

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