title: miR-24 represses metastasis of human osteosarcoma cells by targeting Ack1 via AKT/MMPs pathway.
abstract: The expression levels of the protein tyrosine kinase Ack1 has been reported to be dysregulated in various cancers and involve in oncogenesis and progression. However, the expression and role of Ack1 in osteosarcoma remains unknown. In this study, we found that Ack1 were evidently upregulated in human osteosarcoma tissues and cell lines. In addition, the clinical data showed that high expression level of Ack1 is closely associated with clinical stage and positive distant metastasis, and negatively correlated with overall survival. Then, bioinformatics prediction and luciferase reporter assay indicated Ack1 as a direct target of miR-24, and Ack1 could be downregulated by miR-24 at both the mRNA and protein expression levels. Moreover, Ack1 expression levels were inversely correlated with that of miR-24 in osteosarcoma tissues. Furthermore, functional assay showed that miR-24 significantly suppressed osteosarcoma progression partially mediated by inhibiting Ack1 expression. Finally, western bolt assay revealed that miR-24 regulate AKT/MMPs pathway via Ack1 in osteosarcoma cells. In conclusion, our study demonstrated the suppression of miR-24 on osteosarcoma metastasis by targeting Ack1 via AKT/MMPs pathways, providing a novel strategy for the diagnosis and treatment of osteosarcoma patients.
authors.affiliation: Department of Orthopedic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China. Electronic address: zhendongliu2@163.com.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China. Electronic address: zhitaoliu22@163.com.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China. Electronic address: yuanjunzhang2@163.com.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China. Electronic address: yanli2214@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China. Electronic address: boliu233@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China. Electronic address: kexiangzhang216@163.com.
authors.forename: Kexiang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018716:Molecular Mimicry; D009843:Oligoribonucleotides / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D009843:Oligoribonucleotides; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; C403262:TNK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: AKT/ MMPs pathways; Ack1; Metastasis; Osteosarcoma; miR-24