Papillary thyroid cancer (PTC), the most common thyroid malignancy, has a strong propensity for neck lymph node metastasis, which will increase the risk of local recurrence and decrease the survival in some high-risk groups. Hence, it is essential to set up a reliable biomarker to predict lymph node metastasis. BAG5 is a unique member of the BAG cochaperone family because it consists of more than one BAG domain, which acts as modulator of chaperone activity. In this study, we found that expression of BAG5 was significantly increased in PTC cells and tissues. Neither overexpression nor downregulation of BAG5 altered the proliferation of PTC cells. On the contrary, overexpression of BAG5 significantly promoted, while knockdown of BAG5 significantly decreased migration and invasion of PTC cells. Along with this, fibronectin 1 (FN1) was significantly increased and decreased in cells that overexpress or downregulate BAG5, respectively. Mechanistically, we found that BAG5 modulated FN1 expression at the translational level and promoted invasion via suppression of miR-144-3p, which targeted the 3′ untranslational region (UTR) of FN1 transcript. This study suggests that BAG5 is an important regulator of migration and invasion in PTC cells and may represent a novel therapeutic target for intervening in PTC progression.

甲状腺乳头状癌（PTC）是最常见的甲状腺恶性肿瘤，极易发生颈部淋巴结转移，这将增加局部复发的风险并降低某些高危人群的生存率。因此，建立可靠的生物标志物以预测淋巴结转移至关重要。BAG5是BAG伴侣分子家族的独特成员，因为它由一个以上的BAG结构域组成，可作为伴侣蛋白活性的调节剂。在这项研究中，我们发现BAG5的表达在PTC细胞和组织中显着增加。BAG5的过表达或下调都不会改变PTC细胞的增殖。相反，BAG5的过表达显着促进，而BAG5的敲低则显着降低PTC细胞的迁移和侵袭。伴随着这个 纤连蛋白1（FN1）分别在过度表达或下调BAG5的细胞中显着增加和减少。从机制上讲，我们发现BAG5在翻译水平上调节FN1表达，并通过抑制miR-144-3p来促进侵袭，而miR-144-3p靶向FN1转录本的3'非翻译区（UTR）。这项研究表明BAG5是PTC细胞中迁移和侵袭的重要调节剂，可能代表了干预PTC进展的新型治疗靶点。