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Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

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

Authors: Wendong Ruan, Pei Wang, Shiqing Feng, Yuan Xue, Yulin Li

Published in: Tumor Biology | Issue 3/2016

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Abstract

The long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) has a role in cell proliferation and migration. Angiomotin, encoded by the AMOT gene, is a protein that regulates the migration and organization of endothelial cells. SNHG12 and AMOT have been shown to play a role in a variety of human cancers but have yet to be studied in detail in human osteosarcoma. Tissue samples from primary osteosarcoma (n = 20) and adjacent normal tissues (n = 20), the osteosarcoma cell lines, SAOS-2, MG-63, U-2 OS, and the human osteoblast cell line hFOB (OB3) were studied using Western blot for angiomotin, and quantitative real-time polymerase chain reaction for the expression of SNHG12 and AMOT. The expression of SNHG12 was knocked down using RNA interference. Cell migration assays were performed. Cell apoptosis was studied using flow cytometry. SNHG12 and AMOT messenger RNA (mRNA) expression was upregulated in osteosarcoma tissues and cell lines when compared with normal tissues and cells. Upregulation of AMOT mRNA was associated with upregulation of SNHG12. Knockdown of SNHG12 reduced the expression of angiomotin in osteosarcoma cells and suppressed cell proliferation and migration but did not affect cell apoptosis. This preliminary study has shown that the lncRNA SNHG12 promotes cell proliferation and migration by upregulating AMOT gene expression in osteosarcoma cells in vivo and in vitro. Further studies are recommended to investigate the role of SNHG12 and AMOT expression in tumor cell proliferation and migration and angiogenesis in osteosarcoma and a range of malignant mesenchymal tumors.
Literature
2.
go back to reference Caudill JS, Arndt CA. Diagnosis and management of bone malignancy in adolescence. Adolesc Med State Art Rev. 2007;18:62–78. ix.PubMed Caudill JS, Arndt CA. Diagnosis and management of bone malignancy in adolescence. Adolesc Med State Art Rev. 2007;18:62–78. ix.PubMed
3.
go back to reference Walkley CR, Qudsi R, Sankaran VG, Perry JA, Gostissa M, Roth SI, et al. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 2008;22:1662–76.CrossRefPubMedPubMedCentral Walkley CR, Qudsi R, Sankaran VG, Perry JA, Gostissa M, Roth SI, et al. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 2008;22:1662–76.CrossRefPubMedPubMedCentral
4.
go back to reference O’Day K, Gorlick R. Novel therapeutic agents for osteosarcoma. Expert Rev Anticancer Ther. 2009;9:511–23.CrossRefPubMed O’Day K, Gorlick R. Novel therapeutic agents for osteosarcoma. Expert Rev Anticancer Ther. 2009;9:511–23.CrossRefPubMed
5.
go back to reference Bielack SS, Marina N, Ferrari S, Helman LJ, Smeland S, Whelan JS, et al. Osteosarcoma: the same old drugs or more? J Clin Oncol. 2008;26:3102–3.CrossRefPubMed Bielack SS, Marina N, Ferrari S, Helman LJ, Smeland S, Whelan JS, et al. Osteosarcoma: the same old drugs or more? J Clin Oncol. 2008;26:3102–3.CrossRefPubMed
6.
go back to reference Chou AJ, Geller DS, Gorlick R. Therapy for osteosarcoma: where do we go from here? Paediatr Drugs. 2008;10:315–27.CrossRefPubMed Chou AJ, Geller DS, Gorlick R. Therapy for osteosarcoma: where do we go from here? Paediatr Drugs. 2008;10:315–27.CrossRefPubMed
7.
go back to reference Zhu L, McManus MM, Hughes DPM. Understanding the biology of bone sarcoma from early initiating events through late events in metastasis and disease progression. Front Oncol. 2013;3:230.CrossRefPubMedPubMedCentral Zhu L, McManus MM, Hughes DPM. Understanding the biology of bone sarcoma from early initiating events through late events in metastasis and disease progression. Front Oncol. 2013;3:230.CrossRefPubMedPubMedCentral
9.
10.
go back to reference Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefPubMed Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefPubMed
11.
go back to reference Lai EC. Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet. 2002;30:363–4.CrossRefPubMed Lai EC. Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet. 2002;30:363–4.CrossRefPubMed
14.
go back to reference Wang X, Song X, Glass CK, Rosenfeld MG. The long arm of long noncoding RNAs: roles as sensors regulating gene transcriptional programs. Cold Spring Harb Perspect Biol. 2011;3:a003756.PubMedPubMedCentral Wang X, Song X, Glass CK, Rosenfeld MG. The long arm of long noncoding RNAs: roles as sensors regulating gene transcriptional programs. Cold Spring Harb Perspect Biol. 2011;3:a003756.PubMedPubMedCentral
15.
go back to reference Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.CrossRefPubMed Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.CrossRefPubMed
16.
go back to reference Ding C, Cheng S, Yang Z, Lv Z, Xiao H, Du C, et al. Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells. Int J Mol Sci. 2014;15:4060–76.CrossRefPubMedPubMedCentral Ding C, Cheng S, Yang Z, Lv Z, Xiao H, Du C, et al. Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells. Int J Mol Sci. 2014;15:4060–76.CrossRefPubMedPubMedCentral
17.
go back to reference Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 2013;9:e1003368.CrossRefPubMedPubMedCentral Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 2013;9:e1003368.CrossRefPubMedPubMedCentral
18.
go back to reference Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, et al. Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun. 2013;433:200–6.CrossRefPubMed Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, et al. Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun. 2013;433:200–6.CrossRefPubMed
19.
go back to reference Troyanovsky B, Levchenko T, Månsson G, Matvijenko O, Holmgren L. Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol. 2001;152:1247–54.CrossRefPubMedPubMedCentral Troyanovsky B, Levchenko T, Månsson G, Matvijenko O, Holmgren L. Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol. 2001;152:1247–54.CrossRefPubMedPubMedCentral
20.
go back to reference Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.CrossRefPubMed Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.CrossRefPubMed
22.
go back to reference Huang Y, Liu N, Wang JP, Wang YQ, Yu XL, Wang ZB, et al. Regulatory long non-coding RNA and its functions. J Physiol Biochem. 2012;68:611–8.CrossRefPubMed Huang Y, Liu N, Wang JP, Wang YQ, Yu XL, Wang ZB, et al. Regulatory long non-coding RNA and its functions. J Physiol Biochem. 2012;68:611–8.CrossRefPubMed
23.
go back to reference Li CH, Chen Y. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol. 2013;45:1895–910.CrossRefPubMed Li CH, Chen Y. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol. 2013;45:1895–910.CrossRefPubMed
24.
go back to reference Holmgren L, Ambrosino E, Birot O, Tullus C, Veitonmaki N, Levchenko T, et al. A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth. Proc Natl Acad Sci U S A. 2006;103:9208–13.CrossRefPubMedPubMedCentral Holmgren L, Ambrosino E, Birot O, Tullus C, Veitonmaki N, Levchenko T, et al. A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth. Proc Natl Acad Sci U S A. 2006;103:9208–13.CrossRefPubMedPubMedCentral
25.
go back to reference Levchenko T, Bratt A, Arbiser JL, Holmgren L. Angiomotin expression promotes hemangioendothelioma invasion. Oncogene. 2004;23:1469–73.CrossRefPubMed Levchenko T, Bratt A, Arbiser JL, Holmgren L. Angiomotin expression promotes hemangioendothelioma invasion. Oncogene. 2004;23:1469–73.CrossRefPubMed
26.
go back to reference Yi C, Troutman S, Fera D, Stemmer-Rachamimov A, Avila JL, Christian N, et al. A tight junction-associated Merlin-angiomotin complex mediates Merlin’s regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell. 2011;19:527–40.CrossRefPubMedPubMedCentral Yi C, Troutman S, Fera D, Stemmer-Rachamimov A, Avila JL, Christian N, et al. A tight junction-associated Merlin-angiomotin complex mediates Merlin’s regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell. 2011;19:527–40.CrossRefPubMedPubMedCentral
27.
go back to reference Jiang WG, Watkins G, Douglas-Jones A, Holmgren L, Mansel RE. Angiomotin and angiomotin like proteins, their expression and correlation with angiogenesis and clinical outcome in human breast cancer. BMC Cancer. 2006;6:16.CrossRefPubMedPubMedCentral Jiang WG, Watkins G, Douglas-Jones A, Holmgren L, Mansel RE. Angiomotin and angiomotin like proteins, their expression and correlation with angiogenesis and clinical outcome in human breast cancer. BMC Cancer. 2006;6:16.CrossRefPubMedPubMedCentral
28.
go back to reference Yi C, Shen Z, Stemmer-Rachamimov A, Dawany N, Troutman S, Showe LC, et al. The p130 isoform of angiomotin is required for yap-mediated hepatic epithelial cell proliferation and tumorigenesis. Sci Signal. 2013;6:ra77.CrossRefPubMedPubMedCentral Yi C, Shen Z, Stemmer-Rachamimov A, Dawany N, Troutman S, Showe LC, et al. The p130 isoform of angiomotin is required for yap-mediated hepatic epithelial cell proliferation and tumorigenesis. Sci Signal. 2013;6:ra77.CrossRefPubMedPubMedCentral
29.
go back to reference Arigoni M, Barutello G, Lanzardo S, Longo D, Aime S, Curcio C, et al. A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors. Angiogenesis. 2012;15:305–16.CrossRefPubMedPubMedCentral Arigoni M, Barutello G, Lanzardo S, Longo D, Aime S, Curcio C, et al. A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors. Angiogenesis. 2012;15:305–16.CrossRefPubMedPubMedCentral
30.
go back to reference Bratt A, Birot O, Sinha I, Veitonmaki N, Aase K, Ernkvist M, et al. Angiomotin regulates endothelial cell-cell junctions and cell motility. J Biol Chem. 2005;280:34859–69.CrossRefPubMed Bratt A, Birot O, Sinha I, Veitonmaki N, Aase K, Ernkvist M, et al. Angiomotin regulates endothelial cell-cell junctions and cell motility. J Biol Chem. 2005;280:34859–69.CrossRefPubMed
Metadata
Title
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
Authors
Wendong Ruan
Pei Wang
Shiqing Feng
Yuan Xue
Yulin Li
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4256-7

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