Giant cell tumors of bone (GCTBs) exhibit high recurrence and aggressive bone lytic behavior; but, the mechanism of GCTB progression is largely unknown. In GCTB, we detected abundant levels of miR-125a, which were associated with tumor extension, grade, and recurrence. miR-125a stimulates stromal cell tumorigenicity and growth in vivo by promoting the expression of interleukin-17A (IL-17A) and β-catenin. In contrast, inhibition of miR-125a suppressed stromal cell tumorigenicity and growth. Then, we found that miR-125a stimulates IL-17A by targeting TET2 and Foxp3, and it stimulates β-catenin expression by targeting APC and GSK3β in stromal cells. Furthermore, we identified that IL-17A stimulates miR-125a by activating nuclear factor κB (NF-κB) signaling in stromal cells. Finally, our data show that simultaneous inhibition of IL-17A signaling and miR-125a more significantly inhibits stromal cell growth than miR-125a inhibition alone. miR-125a stimulates the progression of GCTB, and it might represent a useful candidate marker for progression. Simultaneously blocking miR-125a and IL-17A might represent a new therapeutic strategy for GCTB.

骨巨细胞瘤（GCTB）表现出高复发性和积极的溶骨行为。但是，GCTB进展的机制很大程度上未知。在GCTB中，我们检测到大量的miR-125a，这与肿瘤的扩展，分级和复发有关。miR-125a在体内刺激基质细胞致瘤性和生长通过促进白介素-17A（IL-17A）和β-连环蛋白的表达。相反，抑制miR-125a可抑制基质细胞的致瘤性和生长。然后，我们发现miR-125a通过靶向TET2和Foxp3刺激IL-17A，并通过靶向APC和GSK3β在基质细胞中刺激β-catenin表达。此外，我们发现IL-17A通过激活基质细胞中的核因子κB（NF-κB）信号传导来刺激miR-125a。最后，我们的数据表明，与单独的miR-125a抑制相比，同时抑制IL-17A信号和miR-125a抑制基质细胞生长的作用更大。miR-125a刺激了GCTB的进程，它可能代表了进程有用的候选标记。同时阻断miR-125a和IL-17A可能代表了GCTB的新治疗策略。