ABAT, also known as GABA-transaminase, is a key enzyme in the metabolism of gamma-aminobutyric acid (GABA), an important inhibitory neurotransmitter in the brain. It is involved in the GABA shunt pathway, which is crucial for maintaining the balance of GABA levels. This balance is essential for normal neuronal function, as GABA is involved in regulating neuronal excitation and inhibition. Genetic models such as knockout (KO) or conditional knockout (CKO) mouse models can be valuable in studying ABAT's function [3,5].

In liver cancer, inactivation of ABAT was observed at tissue and cell levels, and patients with low ABAT expression had poor prognosis. Overexpressing ABAT could inhibit cancer cell behaviors and suppress tumorigenesis in nude mice, while miR-183-5p, highly expressed in liver cancer, could target and downregulate ABAT expression [1]. In myelodysplastic syndrome, ABAT gene interference increased the sensitivity of HL-60 and THP-1 cells to hypomethylating agents (HMAs) treatment, while overexpression decreased its sensitivity. The downregulation of ABAT gene expression could activate the CXCR4/mTOR signaling pathway related to HMAs sensitivity [2]. In clear cell renal cell carcinoma (ccRCC), downregulated ABAT expression was observed, and low expression was correlated with poor survival. Overexpression of ABAT significantly attenuated cell proliferation and migration [4].

In conclusion, ABAT plays a vital role in regulating GABA metabolism and is important for normal neuronal function. Model-based research, especially in cancer and myelodysplastic syndrome, has revealed its significance in tumorigenesis and drug sensitivity. These findings provide insights into potential therapeutic targets for related diseases.

References:

1. Han, Hui, Zhou, Shenkang, Chen, Gengzhen, Lu, Yandi, Lin, Hui. 2021. ABAT targeted by miR-183-5p regulates cell functions in liver cancer. In The international journal of biochemistry & cell biology, 141, 106116. doi:10.1016/j.biocel.2021.106116. https://pubmed.ncbi.nlm.nih.gov/34742920/

2. Zhao, Guangjie, Li, Shuang, Wang, Qian, Wang, Wei, Wang, Xiaoqin. 2022. ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling. In Cell death discovery, 8, 398. doi:10.1038/s41420-022-01170-7. https://pubmed.ncbi.nlm.nih.gov/36163180/

3. Koenig, Mary Kay, Bonnen, Penelope E. 2018. Metabolomics Profile in ABAT Deficiency Pre- and Post-treatment. In JIMD reports, 43, 13-17. doi:10.1007/8904_2018_94. https://pubmed.ncbi.nlm.nih.gov/29480352/

4. Lu, Jun, Chen, Zhan, Zhao, Hu, Chen, Shushang, Shao, Jichun. 2020. ABAT and ALDH6A1, regulated by transcription factor HNF4A, suppress tumorigenic capability in clear cell renal cell carcinoma. In Journal of translational medicine, 18, 101. doi:10.1186/s12967-020-02268-1. https://pubmed.ncbi.nlm.nih.gov/32093682/

5. Feng, Yan, Wei, Zi-Han, Liu, Chao, Zhang, Chu-Chu, Deng, Yan-Chun. 2022. Genetic variations in GABA metabolism and epilepsy. In Seizure, 101, 22-29. doi:10.1016/j.seizure.2022.07.007. https://pubmed.ncbi.nlm.nih.gov/35850019/