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Tumor Biology

, Volume 37, Issue 10, pp 13403–13412 | Cite as

Long noncoding RNA BCAR4 promotes osteosarcoma progression through activating GLI2-dependent gene transcription

  • Fenyong Chen
  • Jiadong Mo
  • Li ZhangEmail author
Original Article

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.

Keywords

Long noncoding RNA Osteosarcoma Proliferation Metastasis GLI2 pathway 

Notes

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2016_5256_Fig7_ESM.gif (13 kb)
Figure S1

Depletion of BCAR4 does not regulate normal osteoblast cells proliferation. a The expression of BCAR4 after transfection of BCAR4 specific shRNAs into hFOB 1.19 cells. b The effects of BCAR4 depletion on hFOB 1.19 cells proliferation were assessed using the CCK-8 assay, and the relative number of cells to 0 h is presented. Data are shown as the mean ± SD from at least three independent experiments. **P < 0.01 by Student’s t-test. (GIF 13 kb)

13277_2016_5256_MOESM1_ESM.tif (155 kb)
High Resolution Image (TIFF 155 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Orthopaedics, Union HospitalFujian Medical UniversityFuzhouChina
  2. 2.College of Orthopaedics and TraumatologyFujian University of Traditional Chinese MedicineFuzhouChina

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