MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF.
MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF.
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DOI：
10.18632/oncotarget.13747
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发表时间：
2017-01-10
期刊：
影响因子：
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通讯作者：
Chen G
中科院分区：
文献类型：
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作者：
Wang P;Meng X;Huang Y;Lv Z;Liu J;Wang G;Meng W;Xue S;Zhang Q;Zhang P;Chen G
据报道，miR-497在许多类型的癌症的肿瘤发展和进展中起关键作用。因此，我们研究了miR-497在甲状腺癌中的功能和潜在机制。我们发现miR-497在甲状腺癌组织中表达下调，并且miR-497水平与晚期临床分期和淋巴结转移呈负相关。过表达的miR-497在体外抑制甲状腺癌细胞增殖、集落形成、迁移和侵袭，并在体内抑制肿瘤发生。此外，脑源性神经营养因子（BDNF），一种已知的致癌基因，被证实是甲状腺癌细胞中miR-497的直接靶点。miR-497过表达在体外和体内抑制BDNF表达及其下游通路（PI 3 K/AKT）。在人类甲状腺癌标本中，BDNF水平上调，并与miR-497水平呈负相关。拯救实验表明，BDNF的强制过表达有效地逆转了miR-497的肿瘤抑制功能。这些结果表明，miR-497是一种甲状腺癌肿瘤抑制因子，通过抑制BDNF发挥作用。
miR-497 reportedly plays critical roles in tumor development and progression in many types of cancers. We therefore investigated the function and underlying mechanism of miR-497 in thyroid cancer. We found that miR-497 is downregulated in thyroid cancer tissues, and that miR-497 levels are negatively correlated with advanced clinical stage and lymph node metastasis. Overexpressed miR-497 suppressed thyroid cancer cell proliferation, colony formation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo. Moreover, brain-derived neurotrophic factor (BDNF), a known oncogene, was confirmed as a direct target of miR-497 in thyroid cancer cells. miR-497 overexpression suppressed BDNF expression and its downstream pathway(PI3K/AKT)in vitro and in vivo. BDNF levels were upregulated and inversely correlated with miR-497 levels in human thyroid cancer specimens. Rescue experiments showed that forced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-497. These results show that miR-497 is a thyroid cancer tumor suppressor that acts by repressing BDNF.