MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF

Peisong Wang; Xianying Meng; Yan Huang; Zhi Lv; Jia Liu; Guimin Wang; Wei Meng; Shuai Xue; Qiang Zhang; Pengju Zhang; Guang Chen

doi:10.18632/oncotarget.13747

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MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF

Peisong Wang, Xianying Meng, Yan Huang, Zhi Lv, Jia Liu, Guimin Wang, Wei Meng, Shuai Xue, Qiang Zhang, Pengju Zhang and Guang Chen _

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Oncotarget. 2017; 8:2825-2834. https://doi.org/10.18632/oncotarget.13747

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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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MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF

Abstract