Although GABA and GABA receptors function as an inhibitory neurotransmitter in the mature CNS, abnormal levels of gene and protein expression of some GABA receptor subunits have been detected in many malignant tumors, such as π subunit in pancreatic cancer. This indicates that GABAergic system may play an important role in the pathogenesis and development of malignant tumors, and their expression levels are important for prognosis.
A research to be published in the World Journal of Gastroenterology on December 21,2008 addresses a new finding about this hotpoint. The research team led by Prof. Li from Cancer Institute of Central South University used in silico databases to identify genes that were overexpressed in HCC. In this way, they identified the overexpression of GABA receptor α3 subunit (GABRA3) in HCC cells. Knockdown of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth, suggesting its role in HCC cell viability. They also determined the in vitro and in vivo effect of GABA on the proliferation of GABRA3-positive cell lines, and found that GABA increased HCC growth in a dose-dependent manner. Notably, the addition of GABA into the cell culture medium promoted the proliferation of GABRA3-expressing HepG2 cells, but not GABRA3-knockdown HepG2 cells. That means GABA stimulates HepG2 cell growth through GABRA3.
These findings highlight the importance of elucidating the role GABAergic activity play in the pathogenesis of HCC. GABA and GABRA3 could play important roles in HCC development and progression and can be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.