Fig. 3: MCT4 and LINC01711 play a critical role in lactate secretion dysregulation of FAP⁺ CAFs.

A The result of RT-qPCR detecting the expression of the Solute Carrier family (SLC16As) in FAP⁺ CAFs (n = 3 biological repeats). The P-value was calculated by two-tailed unpaired t-test. B The result of western blotting indicating the expression of MCT4 in FAP⁺ CAFs and the efficiency of si-MCT4. C The extracellular lactate production level significantly decreased in FAP⁺ CAFs transfected si-MCT4 (n = 3 biological repeats). The P-value was calculated by two-tailed unpaired t-test. D Flow chart of in vivo co-culture model. VB124 (30 mg/kg) was orally used for MCT4 inhibition daily. E Representative image of subcutaneous tumors. n = 5 biological repeats. F Tumor volume of subcutaneous tumors (n = 5 biological repeats, the P-value was determined by two-way ANOVA with Tukey’s multiple comparison test). G Tumor weight of subcutaneous tumors (n = 5 biological repeats, the P-value was calculated by two-tailed unpaired t-test). H The lactate production level of subcutaneous tumors (n = 5 biological repeats, the P-value was calculated by two-tailed unpaired t-test). I Representative image of FAP and CD8 immunofluorescence in subcutaneous tumors. Scale bars: 2000 μm; 100 μm. J GSEA analysis on RNA-sequence data of FAP⁺ CAFs vs FAP^- CAFs. n = 3 biological repeats. K Volcano map of RNA-sequence data in FAP⁺ CAFs and FAP^- CAFs. n = 3 biological repeats. L Representative image of FAP and CD8 immunofluorescence and LINC01711 fluorescence in situ hybridization (FISH) in TMA cohort (n = 56). Scale bars: 100 μm. M–O Spearman correlation analysis between LINC01711 FISH and FAP, CD8 immunofluorescence in TMA cohort (n = 56). P The si-LINC01711 signature was positively correlated with the infiltration of CD8⁺ T cells, as inferred by xCell, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT, and CIBERSORT-ABS in the TCGA cohorts. All the results were shown as mean ± S.E.M. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.