According to the latest epidemiological investigation, lung adenocarcinoma (LUAD) is one of the most fatal cancer among both men and women. Despite continuous advancements in treatment approaches in recent years, the prognosis for LUAD remains relatively poor. Given the crucial role of the solute carrier (SLC) family in maintaining cellular energy metabolism stability, we conducted a comprehensive analysis of the association between SLC genes and LUAD prognosis. In the present study, we identified 71 genes among the SLC family members, of which 32 were downregulated and 39 were upregulated in LUAD samples. Based on these differentially expressed genes, a prognostic risk scoring model was established that was composed of five genes (SLC16A7, SLC16A4, SLC16A3, SLC12A8, and SLC25A15) and clinical characteristics; this model could effectively predict the survival and prognosis of patients in the cohort. Notably, SLC2A1, SLC25A29, and SLC27A4 were identified as key genes associated with survival and tumor stage. Further analysis revealed that SLC25A29 was underexpressed in LUAD tissue and regulated the phenotype of endothelial cells. Endothelial cell proliferation and migration increased and apoptosis decreased with a decrease in SLC25A29 expression. Investigation of the upstream regulatory mechanisms of SLC25A29 revealed that SLC25A29 expression gradually decreased as the lactate concentration increased. This phenomenon suggested that the expression of SLC25A29 may be related to lactylation modification. ChIP-qPCR experiments confirmed the critical regulatory role played by H3K14la and H3K18la modifications in the promoter region of SLC25A29. In conclusion, this study confirmed the role of SLC family genes in LUAD prognosis and revealed the role of SLC25A29 in regulating endothelial cell phenotypes. These study results provided important clues to further understand LUAD pathogenesis and develop appropriate therapeutic strategies. Solute carrier family effectively predict the prognosis of LUAD patients.Lactic acid decreases SLC25A29 transcription in endothelial cell.Lactic acid in endothelial cells is mainly derived from the tumor microenvironment.The decreased SLC25A29 expression is associated with H3K14la and H3K18la modifications.Lowering SLC25A29 increases endothelial cell proliferation and migration.
基金：
This study was financially supported by the National Natural Science Foundation of China (Grant Nos. 81772477, 81201848, 81700089, 82270104 and 82173684); the Natural Science Foundation of Hubei Province of China (Grant No. 2021CFB355).
第一作者单位：[1]Huazhong Univ Sci & Technol,Dept Resp & Crit Care Med,Key Lab Pulm Dis,Hlth Minist,Tongji Hosp,Tongji Med Coll,Wuhan 430030,Peoples R China
通讯作者：
通讯机构：[1]Huazhong Univ Sci & Technol,Dept Resp & Crit Care Med,Key Lab Pulm Dis,Hlth Minist,Tongji Hosp,Tongji Med Coll,Wuhan 430030,Peoples R China[2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Geriatr,Wuhan 430030,Peoples R China
推荐引用方式(GB/T 7714)：
Zheng Pengdou,Mao Zhenyu,Luo Miao,et al.Comprehensive bioinformatics analysis of the solute carrier family and preliminary exploration of SLC25A29 in lung adenocarcinoma[J].CANCER CELL INTERNATIONAL.2023,23(1):doi:10.1186/s12935-023-03082-7.
APA：
Zheng, Pengdou,Mao, Zhenyu,Luo, Miao,Zhou, Ling,Wang, Lingling...&Wei, Shuang.(2023).Comprehensive bioinformatics analysis of the solute carrier family and preliminary exploration of SLC25A29 in lung adenocarcinoma.CANCER CELL INTERNATIONAL,23,(1)
MLA：
Zheng, Pengdou,et al."Comprehensive bioinformatics analysis of the solute carrier family and preliminary exploration of SLC25A29 in lung adenocarcinoma".CANCER CELL INTERNATIONAL 23..1(2023)
