BAG5 promotes invasion of papillary thyroid cancer cells via upregulation of fibronectin 1 at the translational level.

ABSTRACT

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.