Abstract
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.
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References
Siclari VA, Qin L (2010) Targeting the osteosarcoma cancer stem cell. J Orthop Surg Res 5:78. doi:10.1186/1749-799X-5-78
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
Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30. doi:10.3322/caac.21332
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
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
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
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
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
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
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
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
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
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 8:2994–3000
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
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) 40:426–436
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
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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.
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Liu, SH., Zhu, JW., Xu, HH. et al. A novel antisense long non-coding RNA SATB2-AS1 overexpresses in osteosarcoma and increases cell proliferation and growth. Mol Cell Biochem 430, 47–56 (2017). https://doi.org/10.1007/s11010-017-2953-9
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DOI: https://doi.org/10.1007/s11010-017-2953-9