Slc50a1, a member of the SLC family, is a novel sugar transporter and membrane protein [2]. As the only member of the SWEET class of glucose uniporters in the human genome, it is involved in glucose transmembrane transport [3]. Its associated pathways likely relate to carbohydrate and glucose metabolism, which are of great biological importance in normal physiological functions and disease processes. Genetic models, such as KO/CKO mouse models, could potentially be valuable in further exploring its functions.

In hepatocellular carcinoma (HCC), Slc50a1 is significantly upregulated, correlated with unfavorable prognosis. It can regulate cellular glycolysis and the cell cycle, promoting HCC cell proliferation and reducing apoptosis, while also enhancing resistance to drugs like doxorubicin (DOX) and 2-DG. The m6A methyltransferase METTL3 mediates its methylation modification, which is recognized by IGF2BP2, promoting its stability and translational expression [1].

In breast cancer, Slc50a1 mRNA and serum levels are upregulated. Serum levels can discriminate between breast cancer patients and healthy women, and its protein expression is associated with estrogen receptor and HER2 status. It is also a potential independent prognostic factor, with higher levels related to unfavorable 3-year outcomes in high-grade breast cancer patients [2].

In a study of early-onset Parkinson's disease in the Chinese population, 58 rare variants were identified in Slc50a1, but no significant associations were found at the allele or gene level [4].

In Pakistani families with non-syndromic intellectual disability, a novel homozygous variant (c.245 T > C; p.Leu82Pro) was found in the Slc50a1 gene, with in-silico studies suggesting a drastic effect on protein structure and interaction properties [5].

In cutaneous T-cell lymphomas, an alternative splicing event related to Slc50a1 was identified in association with histone deacetylase inhibitor resistance or sensitivity [6].

In conclusion, Slc50a1 plays important roles in multiple disease conditions. In cancer, especially HCC and breast cancer, it is associated with tumor-related processes such as proliferation, apoptosis, and drug resistance, and serves as a potential diagnostic and prognostic biomarker. In addition, it may be involved in neurological disorders like non-syndromic intellectual disability. The study of Slc50a1 using genetic models like KO/CKO mouse models could further clarify its functions in these diseases, providing insights for potential therapeutic strategies.

References:

1. Wang, Ganggang, Jin, Wenzhi, Zhang, Lianmei, Zhou, Zhijie, Wang, Xiaoliang. 2024. SLC50A1 inhibits the doxorubicin sensitivity in hepatocellular carcinoma cells through regulating the tumor glycolysis. In Cell death discovery, 10, 495. doi:10.1038/s41420-024-02261-3. https://pubmed.ncbi.nlm.nih.gov/39695152/

2. Wang, Yu, Shu, Yao, Gu, Congyang, Fan, Yu. 2019. The novel sugar transporter SLC50A1 as a potential serum-based diagnostic and prognostic biomarker for breast cancer. In Cancer management and research, 11, 865-876. doi:10.2147/CMAR.S190591. https://pubmed.ncbi.nlm.nih.gov/30697078/

3. Wright, Ernest M. . Glucose transport families SLC5 and SLC50. In Molecular aspects of medicine, 34, 183-96. doi:10.1016/j.mam.2012.11.002. https://pubmed.ncbi.nlm.nih.gov/23506865/

4. Li, ChunYu, Ou, RuWei, Chen, YongPing, Wu, Ying, Shang, HuiFang. 2021. Mutation analysis of seven SLC family transporters for early-onset Parkinson's disease in Chinese population. In Neurobiology of aging, 103, 152.e1-152.e6. doi:10.1016/j.neurobiolaging.2021.02.022. https://pubmed.ncbi.nlm.nih.gov/33781609/

5. Ahmed, Iftikhar, Muzammal, Muhammad, Khan, Muzammil Ahmad, Alam, Khurshid, Mir, Asif. 2023. Identification of Four Novel Candidate Genes for Non-syndromic Intellectual Disability in Pakistani Families. In Biochemical genetics, 62, 2571-2586. doi:10.1007/s10528-023-10556-w. https://pubmed.ncbi.nlm.nih.gov/37985543/

6. Yu, Shirong, Zhang, Jingzhan, Ding, Yuan, Kang, Xiaojing, Pu, Xiongming. 2022. Genome-wide identification of alternative splicing associated with histone deacetylase inhibitor in cutaneous T-cell lymphomas. In Frontiers in genetics, 13, 937623. doi:10.3389/fgene.2022.937623. https://pubmed.ncbi.nlm.nih.gov/36147491/