title: The TAZ-miR-224-SMAD4 axis promotes tumorigenesis in osteosarcoma.
abstract: Transcriptional co-activator with PDZ-binding motif (TAZ) is a downstream effector of the Hippo signaling pathway that participates in tumorigenesis. The aim of this study was to identify the miRNA counterpart for TAZ and elucidate the mechanism underlying the tumorigenic effect of TAZ. We demonstrated that TAZ is upregulated in osteosarcoma (OS) tissues and cell lines, and that TAZ overexpression can induce cell migration, invasion and proliferation. Moreover, miRNA-224 (miR-224), a TAZ phenocopy that functions downstream of TAZ, was found to be upregulated with TAZ overexpression. Further, a mechanistic study revealed that miR-224 functions by inhibiting the tumor suppressor, SMAD4, to support the proliferation and migration of OS cells. Our findings indicate that targeting TAZ and miR-224 could be a promising approach for the treatment of OS.
authors.affiliation: Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Kangmao
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Biochemistry, College of Life Science, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Menglu
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Shunwu
authors.initials: S
authors.lastname: Fan
mesh_terms: D000217:Acyltransferases; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C546140:MIRN224 microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human