Th9 cells are a defined CD4+ helper T cell subgroup found to promote or suppress oncogenesis in a context-dependent manner. How microRNAs (miRNAs) shape Th9 cell functionality, however, remains to be studied. Herein, we determined that miR-143/145 is downregulated during Th9 differentiation. When these miRNAs were upregulated, this inhibited Th9 differentiation, proliferation, and IL-9 production. Overexpressing miR-143/145 in Th9 cells further suppressed NFATc1 expression at the protein and mRNA level, whereas the opposite phenotype was observed when miR-143/145 was downregulated in these cells. NFATc1 silencing markedly inhibited Th9 cell differentiation, whereas overexpressing this transcription factor was sufficient to reverse miR-143/145-associated phenotypes in these cells. These findings thus indicate that the ability of miR-143/145 to inhibit Th9 cell differentiation is attributable to their ability to target and suppress NFATc1 expression. Overall, our results highlight a novel mode of action whereby miR-143/145 controls Th9 differentiation, suggesting that this pathway may be amenable to therapeutic targeting in the context of anti-cancer treatment in the future.

Th9细胞是定义的CD4 +辅助性T细胞亚组，被发现以上下文依赖的方式促进或抑制肿瘤发生。microRNA（miRNA）如何塑造Th9细胞功能，还有待研究。在本文中，我们确定在Th9分化过程中miR-143 / 145被下调。当这些miRNA上调时，这会抑制Th9的分化，增殖和IL-9的产生。在Th9细胞中过表达miR-143 / 145进一步抑制了NFATc1在蛋白质和mRNA水平上的表达，而当在这些细胞中下调miR-143 / 145时观察到相反的表型。NFATc1沉默显着抑制Th9细胞分化，而过表达该转录因子足以逆转这些细胞中与miR-143 / 145相关的表型。因此，这些发现表明，miR-143 / 145抑制Th9细胞分化的能力归因于其靶向和抑制NFATc1表达的能力。总体而言，我们的结果突出了一种新的作用方式，其中miR-143 / 145控制Th9分化，这表明该途径可能在未来的抗癌治疗中适合治疗性靶向。