Slc27a3, a solute carrier family 27 member 3, functions as an acyl-CoA ligase, catalyzing the formation of acyl-CoA, which is involved in fatty acid oxidation, lipid synthesis, and lipid metabolism-related pathways [1]. It is highly expressed in lipid-rich tumors like clear cell renal cell carcinoma (ccRCC) and is associated with various biological processes such as mitophagy, immune cell infiltration, and fatty acid transport, thus being of great biological importance. Genetic models, especially gene-knockout (KO) mouse models, can be valuable for studying its functions.

In ccRCC, SLC27A3 is up-regulated in pazopanib-resistant cells and predicts poor prognosis. Knockdown of SLC27A3 in vitro and in vivo suppressed lipid droplet (LD) accumulation and mitophagy, and overcame pazopanib resistance. SLC27A3-mediated acyl-CoA oxidation in mitochondria leads to mitochondrial membrane potential decrease, reactive oxygen species (ROS) production, and subsequent activation of PINK1/Parkin-mediated mitophagy [1]. In chronic obstructive pulmonary disease (COPD), SLC27A3 was identified as a diagnostic biomarker. In COPD mouse models, knockdown of SLC27A3 repressed the JAK2/STAT3 pathway, decreased lung inflammation, improved Th17/Treg balance, and enhanced lung function [2,3].

In summary, SLC27A3 plays a crucial role in lipid metabolism, mitophagy, and immune-related processes. Findings from KO models in ccRCC and COPD mouse models have revealed its significance in drug resistance and disease progression in these specific disease areas, highlighting its potential as a therapeutic target for ccRCC and COPD treatment [1,2,3].

References:

1. Lu, Dingheng, Li, Yuxiao, Niu, Xinyang, Ma, Xueyou, Liu, Ben. 2024. STAT2/SLC27A3/PINK1-Mediated Mitophagy Remodeling Lipid Metabolism Contributes to Pazopanib Resistance in Clear Cell Renal Cell Carcinoma. In Research (Washington, D.C.), 7, 0539. doi:10.34133/research.0539. https://pubmed.ncbi.nlm.nih.gov/39600540/

2. Zhang, Yuepeng, Xia, Rongyao, Lv, Meiyu, Jiang, Yanan, Jin, Shoude. 2022. Machine-Learning Algorithm-Based Prediction of Diagnostic Gene Biomarkers Related to Immune Infiltration in Patients With Chronic Obstructive Pulmonary Disease. In Frontiers in immunology, 13, 740513. doi:10.3389/fimmu.2022.740513. https://pubmed.ncbi.nlm.nih.gov/35350787/

3. Li, Xiaoping, Liu, Ji, Jing, Zehui, Li, Shuxia. 2025. SLC27A3 downregulation restores Th17/Treg balance and alleviates COPD via JAK2/STAT3 pathway inhibition. In Allergologia et immunopathologia, 53, 91-98. doi:10.15586/aei.v53i1.1215. https://pubmed.ncbi.nlm.nih.gov/39786880/