Project description:miRNA sponge, a special class of miRNA target, has been emerging as a pivotal player in miRNA mediated regulatory network. Currently, the identified miRNA sponge genes mostly act on sequestering conserved miRNAs (e.g. miR-7, miR-145), however, the existence, potential function and evolutionary process of miRNA sponge genes for species-specific miRNA, especially for human specific miRNA, are largely unknown. In this study, we conducted a systematic analysis including sponge gene identification and subsequent function and evolutionary analyses for an authentic human-specific miRNA, miR-941.
Project description:Exosomal and cellular miRNA expression levels were measured using a microRNA chip array or quantitative reverse transcription PCR (qRT-PCR). miR-24-3p was enriched in T-EXOs from the sera of NPC patients and NPC cells, which was correlated with worse disease-free survival (DFS). Exosomes (miR-24-3p-sponge-EXO) released from miR-24-3p-sponge-TW03 cells failed to inhibit T-cell proliferation and Th1 and Th17 differentiation or to induce Treg differentiation in vitro, compared with controlNC -sponge-EXO. Mechanistic analyses revealed that in miR-24-3p-sponge-EXO-treated T-cells, P-ERK, P-STAT1 and P-STAT3 were up-regulated, whereas P-STAT5 was down-regulated compared with controlNC-sponge-EXO-treated T-cells. FGF11 was identified as a direct target gene of miR-24-3p through in vivo and in vitro assessments. More importantly, the T-EXOs repressed FGF11 expression in T-cells during proliferation and differentiation. Interestingly, when FGF11 expression in T-cells was blocked, miR-24-3p-sponge-EXOs impeded shFGF11-T-cell proliferation and Th1 and Th17 differentiation but induced Treg differentiation, like controlNC-sponge-EXO. When FGF11 was knocked down in miR-24-3p-sponge-EXO-treated T-cells, neither P-ERK, P-STAT1 and P-STAT3 up-regulation or P-STAT5 down-regulation occurred. Interestingly, FGF11 expression in tumor-infiltrating lymphocytes (TILs) was significantly and positively correlated with the number of CD4+ and CD8+ TILs and predicted favorable DFS of the patients (p < 0.05).