Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110122, China; Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China; Department of Thyroid Surgery, The 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
Clinical Medical Laboratory, The 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
Biochim Biophys Acta Mol Cell Res. 2020 Sep;1867(9):118715. doi: 10.1016/j.bbamcr.2020.118715. Epub 2020 Apr 8.
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，具有很强的颈部淋巴结转移倾向，这会增加局部复发的风险，并降低某些高危人群的生存率。因此，建立一个可靠的生物标志物来预测淋巴结转移至关重要。BAG5 是 BAG 共伴侣家族中的一个独特成员，因为它由一个以上的 BAG 结构域组成，作为伴侣活性的调节剂。在本研究中，我们发现 BAG5 在 PTC 细胞和组织中的表达显著增加。BAG5 的过表达或下调均未改变 PTC 细胞的增殖。相反，BAG5 的过表达显著促进了 PTC 细胞的迁移和侵袭，而 BAG5 的敲低则显著降低了其迁移和侵袭。与此同时，纤连蛋白 1（FN1）在过表达或下调 BAG5 的细胞中分别显著增加和减少。在机制上，我们发现 BAG5 在翻译水平上调节 FN1 的表达，并通过抑制 miR-144-3p 来促进侵袭，miR-144-3p 靶向 FN1 转录本的 3'非翻译区（UTR）。本研究表明，BAG5 是 PTC 细胞迁移和侵袭的重要调节因子，可能代表干预 PTC 进展的新的治疗靶点。
