title: MicroRNA-204 inhibits proliferation, migration, invasion and epithelial-mesenchymal transition in osteosarcoma cells via targeting Sirtuin 1.
abstract: MicroRNAs (miRs) play crucial roles in tumorigenesis by directly suppressing the protein expression levels of their target genes. miR-204 has been suggested to act as a tumor suppressor in several types of human cancer. However, the exact role of miR-204 in osteosarcoma (OS) remains undetermined. In the present study, we aimed to investigate the effects of miR-204 on OS cell proliferation, migration and invasion, as well as the underlying molecular mechanisms. We found that the expression of miR-204 was frequently downregulated in four OS cell lines compared to the level in normal human osteoblast cells. Moreover, overexpression of miR-204 significantly inhibited the proliferation, migration and invasion of OS cells. Based on bioinformatics prediction and a luciferase reporter assay, we identified Sirtuin 1 (Sirt1) as a direct target gene of miR-204 in OS Saso-2 cells. Moreover, the protein expression of Sirt1 was negatively mediated by miR-204 in the OS cells. siRNA-mediated knockdown of Sirt1 also inhibited the proliferation, migration and invasion of the OS cells. Moreover, overexpression of Sirt1 reversed the inhibitory effect of miR-204 overexpression on the proliferation, migration and invasion of the OS cells. In addition, after miR-204 overexpression or Sirt1 knockdown in OS cells, the expression of E-cadherin was increased, while the N-cadherin protein level was reduced. Based on these findings, we suggest that miR-204 inhibits the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of OS cells by directly targeting Sirt1.
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: The Second Department of Orthopedics, The First Affiliated Hospital of Jishou University, Jishou, Hunan 416000, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jifang
authors.initials: J
authors.lastname: Wen
mesh_terms: D020413:3' Untranslated Regions; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; C447939:SIRT1 protein, human; D056564:Sirtuin 1