title: microRNA-106b-mediated down-regulation of C1orf24 expression induces apoptosis and suppresses invasion of thyroid cancer.
abstract: We previously showed that C1orf24 expression is increased in thyroid carcinomas. Nonetheless, the mechanism underlying C1orf24 deregulation is not fully understood. It has been widely demonstrated that microRNAs are involved in post-transcriptional gene regulation in several diseases, including cancer. Using in silico prediction approach, five microRNAs that bind to the 3'-untranslated region (3'-UTR) of C1orf24 were identified. The expression of two selected microRNAs (miR-17-5p, miR-106b) and the expression of C1orf24 were tested in 48 benign and malignant thyroid lesions and in five thyroid carcinoma cell lines. miR-106b was down-regulated in thyroid cancer specimens and thyroid carcinoma cell lines, while C1orf24 expression was markedly increased. To demonstrate that miR-106b reduces C1orf24 expression, follicular (WRO) and papillary (TPC1) thyroid carcinoma cell lines were transiently transfected with miR-106b mimic. Ectopic expression of the miR-106b mimic significantly inhibits C1orf24 mRNA and protein expression in both WRO and TPC1 cells. Dual-luciferase report assays demonstrated that miR-106b directly targets C1orf24 by binding its 3'-UTR. Moreover, miR-106b-mediated down-regulation of C1orf24 expression increased apoptosis and inhibited migration. We additionally demonstrated that siRNA against C1orf24 significantly decreased its expression, inhibited cell migration and cell cycle progression while induced apoptosis. In summary, our findings not only provide new insights into molecular mechanism associated with C1orf24 overexpression in thyroid carcinomas but also show that C1orf24 might increase proliferation and cell migration. Thus, decreasing C1orf24 levels, by restoring miR-106b function, may have therapeutic implications.
authors: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, SP, Brazil.
authors: Gianna
authors: G
authors: Carvalheira
authors: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, SP, Brazil.
authors: Bruno Heidi
authors: BH
authors: Nozima
authors: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, SP, Brazil.
authors: Janete Maria
authors: JM
authors: Cerutti
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051017:Apoptosis Regulatory Proteins
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D009363:Neoplasm Proteins; C542541:MIRN106 microRNA, human; C516108:NIBAN1 protein, human; D051017:Apoptosis Regulatory Proteins
keywords: C1orf24; FAM129A; NIBAN; follicular thyroid carcinoma and papillary thyroid carcinoma; miR-106b