title: miR-126 inhibits papillary thyroid carcinoma growth by targeting LRP6.
abstract: microRNA-126 (miR-126) has been reported to play tumor suppressor roles in various types of cancers. Although it has been reported that miR-126 expression is downregulated in papillary thyroid carcinoma (PTC), the precise role and underlying molecular mechanism of miR-126 in PTC remains unclear. Therefore, the aims of the present study were to investigate the role and potential mechanism of miR-126 in tumorigenicity of PTC in vivo and in vitro. We observed that the miR-126 expression level was significantly downregulated in PTC tissue and PTC cell lines, the aberrant expression of miR-126 was correlated with lymph node metastasis, tumor size and TNM stage. We also showed that restoration of miR-126 in PTC cells inhibited cell proliferation, colony formations, migration and invasion, promoted cell apoptosis and cell cycle arrest at G1 stage in vitro, as well as inhibited tumor growth and decreased tumor volume and weight in vivo. Furthermore, low-density lipoprotein receptor‑related protein 6 (LRP6), a regulator of the Wnt/β‑catenin signaling cascade, was identified as a crucial target gene of miR-126. Overexpression of miR-126 inhibited LP6 expression on mRNA and protein levels, and deactivate Wnt/β-catenin signaling pathway. These results suggested that miR-126 functions as a tumor-suppressive miRNA by targeting LRP6 regulating Wnt/β-catenin signaling pathway and represents a therapeutic target for PTC.
authors.affiliation: Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 13033, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 13033, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 13033, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 13033, P.R. China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Surgery, China-Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 13033, P.R. China.
authors.forename: Haishan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 13033, P.R. China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Ma
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D060449:Wnt Signaling Pathway
chemical_list: D020413:3' Untranslated Regions; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C527111:MIRN126 microRNA, human; D035683:MicroRNAs