Research Papers:
MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF
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Abstract
Peisong Wang1, Xianying Meng1, Yan Huang2, Zhi Lv2, Jia Liu1, Guimin Wang1, Wei Meng1, Shuai Xue1, Qiang Zhang1, Pengju Zhang3,*, Guang Chen1,*
1Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China
2Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Jingyue District, Changchun 130033, China
3Jilin Academy of Agricultural Sciences, Nanguan District, Changchun 130000, China
*These authors have contributed equally to this work
Correspondence to:
Guang Chen, email: [email protected]
Pengju Zhang, email: [email protected]
Keywords: miR-497, thyroid cancer, BDNF, tumorigenesis, metastasis
Received: August 23, 2016 Accepted: November 22, 2016 Published: December 01, 2016
ABSTRACT
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.
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