Gammaaminobutyric Acid A Receptor Alpha 3 Subunit is Overexpressed in Lung Cancer

Abstract

The identification of tumor-associated antigens, which are specifically expressed in cancer tissues, is very important for immunotherapy of lung cancer. We have combined the in silico screening and experimental verifying to identify genes that are differently expressed in cancers compared with their corresponding normal tissues. Using these methods, we have identified that GABRA3 gene was overexpressed in lung cancer and rarely expressed in other cancers. Furthermore, GABRA3 protein expression was significantly higher in the lower grade of lung cancer. It may compose functional GABA-gated channel with other subunits. This study demonstrated GABRA3 could be a potential biomarker for diagnosis of lung cancer, and GABAA receptors may play an important role in cancer differentiation.

GABRA3 promotes lymphatic metastasis in lung adenocarcinoma by mediating upregulation of matrix metalloproteinases

“…Liu et al demonstrated that GABR A3 is overexpressed in hepatocellular carcinoma and that GABA promoted hepatocellular carcinoma cell proliferation through overexpression of GABR A3 [16]. Liu et al also reported that GABR A3 is overexpressed in NSCLC tissues, and that the level of GABR A3 expression was associated with the NSCLC grade [11]. Consistent with this observation, we previously showed that higher levels of GABR A3 mRNA are associated with disease progression in NSCLC patients [10].…”

“…Moreover, expression of GABR A3 mRNA was associated with a poor prognosis in patients with NSCLC. Consistent with that observation, Liu et al found that GABR A3 gene is overexpressed in NSCLC [11]. This suggests that dominant expression of the GABR A3 subunit may result in cancer progression.…”

A novel cancer-germline transcript carrying pro-metastatic miR-105 andTET-targeting miR-767 induced by DNA hypomethylation in tumors

“…Among these, we noticed a pair of miRNAs (miR-105 and miR-767), deriving from the first intron of GABRA3 , a gene encoding a receptor subunit for the γ-aminobutyric-acid neurotransmitter. Our interest for these miRNAs was prompted by the fact that, although GABRA3 expression is normally restricted to brain and testis, aberrant transcription of the gene was reported in several tumor types, and was identified as a significant predictor of poor survival in lung cancer patients 9 - 12 . Moreover, GABRA3 is located within a region of the X chromosome (Xq28) that harbors many known CG genes.…”

Gamma-Aminobutyric Acid Binds to GABAB Receptor to Inhibit Cholangiocarcinoma Cells Growth via the JAK/STAT3 Pathway

“…Protein expression was quantified using a visual grading system [5] based on the extent of staining (percentage of positive tumor cells graded on a scale 0-4: 0, none; 1, B10 %; 2, 11-50 %; 3, 51-75 %; 4,[75 %) and the intensity of staining (graded on a scale of 0-3: 0, no staining; 1, weak staining; 2, moderate staining; 3, strong staining). For further analysis, an index value was calculated as the product of the grades of the extent and intensity of staining to define the cutoff value for high expression of the proteins; based on this index, and protein expression was classified into two categories: high (grades 4-12) and low (grades 0-3).…”

“…It acts as either a ionotropic GABA A or GABA C receptor (GABA A R or GABA C R) or as a metabotropic GABA B receptor (GABA B R). Outside the brain, GABA and its receptors have been found in non-neuronal peripheral tissues, such as the gastrointestinal system [4], lung [5], and liver [6], including the biliary tract system [7]. Studies have implicated GABA and its receptors as important players not only in synaptic inhibition, convulsion, pain, depression, and cognition [8], but also in the inhibition of cancer growth and tumor cell migration in, for example, colorectal carcinoma [9] and breast cancer [10].…”