Slc1a3, also known as the glutamate/aspartate transporter, is a member of the glutamate transporter family. It plays a crucial role in the transport of aspartate and glutamate, mainly expressed in brain tissues [4]. It has been implicated in regulating glutamine catabolism and is associated with pathways like p53, NF-κB, and PI3K/AKT [1,3].

Knockdown of Slc1a3 inhibited Newcastle disease virus (NDV) infection, as NDV hijacks Slc1a3-regulated glutaminolysis for its replication [1]. In gastric cancer, its overexpression promoted tumor growth via the PI3K/AKT pathway, and in hepatocellular carcinoma, it was associated with poor prognosis, affecting immune cell infiltration and EMT process [3,6]. In osimertinib-resistant EGFR mutant lung cancer cells, inhibition of Slc1a3 increased drug sensitivity [8]. Also, SLC1A3 was identified as a hub gene in diabetic nephropathy, with diagnostic potential [2]. It has also been associated with hemiplegic migraine [5,7].

In conclusion, Slc1a3 is a significant gene involved in multiple biological processes and disease conditions. Its role in viral replication, cancer progression, and as a diagnostic marker in diseases like diabetic nephropathy has been revealed through functional studies. The study of Slc1a3 using gene-knockdown models provides valuable insights into disease mechanisms, potentially leading to new therapeutic strategies for related diseases.

References:

1. Liu, Panrao, Tang, Ning, Meng, Chunchun, Lin, Shu-Hai, Ding, Chan. . SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism. In Virulence, 13, 1407-1422. doi:10.1080/21505594.2022.2112821. https://pubmed.ncbi.nlm.nih.gov/35993169/

2. Xu, Mingming, Zhou, Hang, Hu, Ping, Liu, Li, Liu, Xiaoqiang. 2023. Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning. In Frontiers in immunology, 14, 1084531. doi:10.3389/fimmu.2023.1084531. https://pubmed.ncbi.nlm.nih.gov/36911691/

3. Xu, Liyi, Chen, Jiamin, Jia, Litao, Awaleh Moumin, Faycal, Cai, Jianting. 2020. SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway. In Journal of cellular and molecular medicine, 24, 14392-14404. doi:10.1111/jcmm.16060. https://pubmed.ncbi.nlm.nih.gov/33145952/

4. Sun, Jianhui, Nagel, Remco, Zaal, Esther A, Berkers, Celia R, Agami, Reuven. 2019. SLC1A3 contributes to L-asparaginase resistance in solid tumors. In The EMBO journal, 38, e102147. doi:10.15252/embj.2019102147. https://pubmed.ncbi.nlm.nih.gov/31523835/

5. Nandyala, Arathi, Shah, Tulsi, Ailani, Jessica. 2023. Hemiplegic Migraine. In Current neurology and neuroscience reports, 23, 381-387. doi:10.1007/s11910-023-01277-z. https://pubmed.ncbi.nlm.nih.gov/37247170/

6. Zhi, Renhou, Fan, Fan. 2024. SLC1A3 is a novel prognostic biomarker associated with immunity and EMT in hepatocellular carcinoma. In Discover oncology, 15, 676. doi:10.1007/s12672-024-01561-5. https://pubmed.ncbi.nlm.nih.gov/39560677/

7. Paucar, Martin, Granberg, Tobias, Lagerstedt-Robinson, Kristina, Nordin, Love, Svenningsson, Per. 2020. SLC1A3 variant associated with hemiplegic migraine and acetazolamide-responsive MRS changes. In Neurology. Genetics, 6, e474. doi:10.1212/NXG.0000000000000474. https://pubmed.ncbi.nlm.nih.gov/32754645/

8. Ochi, Nobuaki, Miyake, Noriko, Takeyama, Masami, Kiura, Katsuyuki, Takigawa, Nagio. 2024. The combined inhibition of SLC1A3 and glutaminase in osimertinib-resistant EGFR mutant cells. In Biochimica et biophysica acta. General subjects, 1868, 130675. doi:10.1016/j.bbagen.2024.130675. https://pubmed.ncbi.nlm.nih.gov/39059510/