Fig. 5: Tumor-derived exosomal miR-222-3p directly targets PANK3 in fibroblasts.

A MiRNAs sequencing of differentially expressed genes between CAFs and NFs. B Differential expression and prognostic analysis of miR-222-3p in the TCGA-KIRC database. C Differential expression of miR-222-3p in patients with or without metastasis in the TCGA-KIRC database. D qRT-PCR assays of miR-222-3p in NF and CAF3. E Univariate and multivariate COX regression analysis of miR-222-3p in the TCGA-KIRC database. F In situ hybridization of miR-222-3p on human ccRCC tissues. Scale bar, 50 μm. G Exosomal miR-222-3p expression from different ccRCC cell lines. H qRT-PCR analysis of miR-222-3p expression of NFs treated with equal quantities of exosomes derived from cRCC cell lines. I Correlation analysis of miR-222-3p and PANK3 expression in the TCGA-KIRC database. J Alteration of miR-222-3p levels in NFs following transfection with miR-222-3p mimic or miR-222-3p inhibitor. K qRT-PCR and immunoblotting assays of PANK3 in NFs transfected with miR-222-3p mimic or NC mimic. L Relative luciferase activity of NFs in the presence of indicated treatments. M Comparison of glucose uptake, GLUT1 expression, total ROS level of NFs transfected with miR-222-3p mimic or NC mimic. N qRT-PCR analysis of pro-inflammatory genes expression of NFs transfected with miR-222-3p mimic or NC mimic. O Immunoblotting assays of α-SMA and FAP in NFs with indicated treatments. Each experiment was performed three times independently and results are presented as mean ± s.d. Student’s t-test was used to analyze the data (*p < 0.05; **p < 0.01; ***p < 0.001).