title: Long noncoding RNA BCAR4 promotes osteosarcoma progression through activating GLI2-dependent gene transcription.
abstract: Despite great advances have been made in the understanding of biology of osteosarcoma, the molecular mechanisms involved in osteosarcoma tumorigenesis and progression are still largely unknown. Long noncoding RNA (lncRNA) is a new type of RNA molecule, which plays pivotal roles in many tumors. lncRNA BCAR4 has been identified as an oncogenetic lncRNA involved in the progression of breast cancer. However, the functions and clinical significances of BCAR4 in osteosarcoma are unknown now. In this study, we found that BCAR4 was significantly upregulated in osteosarcoma tissues. Increased expression of BCAR4 was significantly correlated with large tumor size, advanced Enneking stage, lung metastasis, and poor prognosis. Functional experiments demonstrated that knockdown of BCAR4 inhibits the proliferation and migration of osteosarcoma cell in vitro. Consistently, knockdown of BCAR4 inhibits osteosarcoma tumorigenesis and lung metastasis in vivo. Chromatin isolation by RNA purification assay showed that BCAR4 physically associates with the promoters of GLI2 target genes. The depletion of BCAR4 inhibits the expression of GLI2 target genes and GLI2 reporter luciferase activity in a dose-dependent manner. The expression of BCAR4 and GLI2 target genes is significantly correlated in osteosarcoma tissues. Depletion of DLI2 abolished the effects of BCAR4 on osteosarcoma. Taken together, these findings demonstrated that BCAR4 promotes osteosarcoma progression via activating GLI2-dependent gene transcription and serves as a potential prognostic biomarker and a therapeutic target of osteosarcoma.
authors.affiliation: Department of Orthopaedics, Union Hospital, Fujian Medical University, Fuzhou, 350001, China.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Union Hospital, Fujian Medical University, Fuzhou, 350001, China.
authors.forename: Jiadong
authors.initials: J
authors.lastname: Mo
authors.affiliation: College of Orthopaedics and Traumatology, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. zhanglil626@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D000075746:Zinc Finger Protein Gli2
chemical_list: C553206:BCAR4 non-coding RNA, human; C082593:GLI2 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D000075746:Zinc Finger Protein Gli2
keywords: GLI2 pathway; Long noncoding RNA; Metastasis; Osteosarcoma; Proliferation