Molecular and Cellular Biochemistry

, Volume 430, Issue 1–2, pp 47–56 | Cite as

A novel antisense long non-coding RNA SATB2-AS1 overexpresses in osteosarcoma and increases cell proliferation and growth

  • Si-Hong Liu
  • Jian-Wei Zhu
  • Hui-Hua Xu
  • Gui-Qiang Zhang
  • Yan Wang
  • Ya-Min Liu
  • Jun-Bo Liang
  • Yu-Xuan Wang
  • Yong WuEmail author
  • Qi-Feng GuoEmail author


The knowledge regarding the importance of long non-coding RNAs (lncRNAs), a new class of genes, is very sparse in osteosarcoma. In the present study, we describe the expression profile of lncRNAs in osteosarcomas compared with paired adjacent non-cancerous tissue (n = 7) using microarray analysis. A total of 25,733 lncRNAs were identified in osteosarcoma; 1995 lncRNAs were consistently upregulated and 2226 lncRNAs were consistently under-regulated in all samples analyzed (≥2.0-fold, p < 0.05). We have validated three over-regulated and three under-regulated lncRNAs in patient samples (n = 7). The antisense transcript of SATB2 protein (SATB2-AS1) was identified as one of the upregulated lncRNAs. The SATB2-AS1 is a 3197-bp lncRNA on chromosome 2. This is the first report, where we have documented the increased expression of SATB2-AS1 in osteosarcoma patients and in human osteosarcoma cancer cell lines (U2OS, HOS, MG63). SATB2-AS1 expression was significantly higher in the metastatic tumors compared to non-metastatic tumors. In vitro gain and loss of function approaches demonstrated that SATB2-AS1 regulates cell cycle, cell proliferation, and cell growth. In addition, SATB2-AS1 affects the translational expression of SATB2 gene. Our data demonstrate that an antisense non-coding RNA regulates the expression of its sense gene, and increases the cell growth, therefore pointing the pivotal functions of SATB2-AS1 in osteosarcoma.


LncRNA Osteosarcoma Antisense Cell proliferation Metastasis Cell Cycle 



The National Nature Science Foundation of China (Nos. 31601031, 81272941, 81201864), and The Guangdong Planned Project of Science and Technology (2014A020212009) financially supported the present study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

11010_2017_2953_MOESM1_ESM.tiff (21.4 mb)
Supplementary material 1 (TIFF 21957 KB)
11010_2017_2953_MOESM2_ESM.tiff (14.2 mb)
Supplementary material 2 (TIFF 14546 KB)
11010_2017_2953_MOESM3_ESM.docx (39 kb)
Supplementary material 3 (DOCX 39 KB)


  1. 1.
    Siclari VA, Qin L (2010) Targeting the osteosarcoma cancer stem cell. J Orthop Surg Res 5:78. doi: 10.1186/1749-799X-5-78 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Yan GN, Lv YF, Guo QN (2016) Advances in osteosarcoma stem cell research and opportunities for novel therapeutic targets. Cancer Lett 370:268–274. doi: 10.1016/j.canlet.2015.11.003 CrossRefPubMedGoogle Scholar
  3. 3.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30. doi: 10.3322/caac.21332 CrossRefPubMedGoogle Scholar
  4. 4.
    Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G (2006) Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev 32:423–436. doi: 10.1016/j.ctrv.2006.05.005 CrossRefPubMedGoogle Scholar
  5. 5.
    Kager L, Zoubek A, Potschger U, Kastner U, Flege S, Kempf-Bielack B, Branscheid D, Kotz R, Salzer-Kuntschik M, Winkelmann W, Jundt G, Kabisch H, Reichardt P, Jurgens H, Gadner H, Bielack SS and Cooperative German-Austrian-Swiss Osteosarcoma Study G (2003) Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 21:2011–8. doi: 10.1200/JCO.2003.08.132 CrossRefPubMedGoogle Scholar
  6. 6.
    Bartonicek N, Maag JL, Dinger ME (2016) Long non-coding RNAs in cancer: mechanisms of action and technological advancements. Mol Cancer 15:43. doi: 10.1186/s12943-016-0530-6 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Huynh NP, Anderson B, Guilak F, McAlinden A (2016) Emerging roles for long non-coding RNAs in skeletal biology and disease. Connect Tissue Res. doi: 10.1080/03008207.2016.1194406 PubMedPubMedCentralGoogle Scholar
  8. 8.
    Zhao X, Qu Z, Tickner J, Xu J, Dai K, Zhang X (2014) The role of SATB2 in skeletogenesis and human disease. Cytokine Growth Factor Rev 25:35–44. doi: 10.1016/j.cytogfr.2013.12.010 CrossRefPubMedGoogle Scholar
  9. 9.
    Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Farinas I, Karsenty G, Grosschedl R (2006) SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell 125:971–986. doi: 10.1016/j.cell.2006.05.012 CrossRefPubMedGoogle Scholar
  10. 10.
    Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, Liu YQ, Zhong H, Li H, Xiao T (2013) Microarray expression profile of long non-coding RNAs in human osteosarcoma. Biochem Biophys Res Commun 433:200–206. doi: 10.1016/j.bbrc.2013.02.083 CrossRefPubMedGoogle Scholar
  11. 11.
    Wilusz JE, JnBaptiste CK, Lu LY, Kuhn CD, Joshua-Tor L, Sharp PA (2012) A triple helix stabilizes the 3′ ends of long non-coding RNAs that lack poly(A) tails. Genes Dev 26:2392–2407. doi: 10.1101/gad.204438.112 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ruan W, Wang P, Feng S, Xue Y, Li Y (2016) Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes cell proliferation and migration by upregulating angiomotin gene expression in human osteosarcoma cells. Tumour Biol 37:4065–4073. doi: 10.1007/s13277-015-4256-7 CrossRefPubMedGoogle Scholar
  13. 13.
    Sun XH, Yang LB, Geng XL, Wang R, Zhang ZC (2015) Increased expression of lncRNA HULC indicates a poor prognosis and promotes cell metastasis in osteosarcoma. Int J Clin Exp Pathol 8:2994–3000PubMedPubMedCentralGoogle Scholar
  14. 14.
    Cong M, Li J, Jing R, Li Z (2016) Long non-coding RNA tumor suppressor candidate 7 functions as a tumor suppressor and inhibits proliferation in osteosarcoma. Tumour Biol. doi: 10.1007/s13277-015-4414-y PubMedGoogle Scholar
  15. 15.
    Guo Y, Xiao P, Lei S, Deng F, Xiao GG, Liu Y, Chen X, Li L, Wu S, Chen Y, Jiang H, Tan L, Xie J, Zhu X, Liang S, Deng H (2008) How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim Biophys Sin (Shanghai) 40:426–436CrossRefGoogle Scholar
  16. 16.
    Mahajan N, Bisht D, Dhawan V, Singh S, Minz RW (2010) Transcriptional expression and gelatinolytic activity of matrix metalloproteinases in Henoch-Schonlein purpura. Acta Paediatr 99:1248–1252. doi: 10.1111/j.1651-2227.2010.01781.x CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Si-Hong Liu
    • 1
    • 2
  • Jian-Wei Zhu
    • 2
  • Hui-Hua Xu
    • 2
  • Gui-Qiang Zhang
    • 2
  • Yan Wang
    • 2
  • Ya-Min Liu
    • 2
  • Jun-Bo Liang
    • 2
  • Yu-Xuan Wang
    • 2
  • Yong Wu
    • 3
    Email author
  • Qi-Feng Guo
    • 2
    Email author
  1. 1.Jinan UniversityGuangzhou,People’s Republic of China
  2. 2.Department of Orthopaedics, Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhou,People’s Republic of China
  3. 3.Department of Oncology, Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhouPeople’s Republic of China

Personalised recommendations