title: MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF.
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.
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China.
authors.forename: Peisong
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China.
authors.forename: Xianying
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Jingyue District, Changchun 130033, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Jingyue District, Changchun 130033, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China.
authors.forename: Guimin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Jilin Academy of Agricultural Sciences, Nanguan District, Changchun 130000, China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang District, Changchun 130021, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C559640:MIRN497 microRNA, human; D035683:MicroRNAs
keywords: BDNF; metastasis; miR-497; thyroid cancer; tumorigenesis