Gene expression profiling analysis of osteosarcoma cell lines

Sun,Lu; Li,Jie; Yan,Bing

doi:10.3892/mmr.2015.3958

Gene expression profiling analysis of osteosarcoma cell lines

Authors:
- Lu Sun
- Jie Li
- Bing Yan
View Affiliations

Affiliations: Department of Orthopedics, Shandong Chinese Medical Hospital, Jinan, Shandong 250014, P.R. China
Published online on: June 18, 2015 https://doi.org/10.3892/mmr.2015.3958
Pages: 4266-4272
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteosarcoma (OS) is the most common type of primary bone malignancy and has a poor prognosis. To investigate the mechanisms of osteosarcoma, the present analyzed the GSE28424 microarray. GSE28424 was downloaded from the Gene Expression Omnibus, and included a collective of 19 OS cell lines and four normal bone cell lines, which were used as controls. Subsequently, the differentially expressed genes (DEGs) were screened using the Limma package in Bioconductor. Gene Ontology (GO) and pathway enrichment analysis of the DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery, interactions between the proteins encoded by the DEGs were identified using STRING, and the protein‑protein interaction (PPI) network was visualized using Cytoscape. In addition, modular analysis of the PPI network was performed using the Clique Percolation Method (CPM) in CFinder. A total of 1,170 DEGs were screened, including 530 upreguated and 640 downregulated genes. The enriched functions included organelle fission, immune response and response to wounding. In addition, RPL8 was observed to be involved with the ribosomal pathway in module A of the PPI network of the DEGs. PLCG1, SYK and PLCG2 were also involved in the B‑cell receptor signaling pathway in module B and the Fc‑epsilon RI signaling pathway in module C. In addition, AURKA (degree=39), MAD2L1 (degree=38), CDCA8 (degree=38), BUB1 (degree=37) and MELK (degree=37) exhibited higher degrees of connectivity in module F. The results of the present study suggested that the RPL8, PLCG1, PLCG2, SYK, MAD2L1, AURKA, CDCA8, BUB1 and MELK genes may be involved in OS.

View Figures

View References

1	Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar
2	Ritter J and Bielack SS: Osteosarcoma. Ann Oncol. 21(Suppl 7): vii320–vii325. 2010. View Article : Google Scholar : PubMed/NCBI
3	Stiller CA, Bielack SS, Jundt G and Steliarova-Foucher E: Bone tumours in European children and adolescents, 1978–1997. Report from the automated childhood cancer information system project. Eur J Cancer. 42:2124–2135. 2006. View Article : Google Scholar : PubMed/NCBI
4	Stiller CA, Craft AW and Corazziari I: EUROCARE Working Group: Survival of children with bone sarcoma in Europe since 1978: results from the EUROCARE study. Eur J Cancer. 37:760–766. 2001. View Article : Google Scholar : PubMed/NCBI
5	Yang J, Yang D, Sun Y, et al: Genetic amplification of the vascular endothelial growth factor (VEGF) pathway genes, including VEGFA, in human osteosarcoma. Cancer. 117:4925–4938. 2011. View Article : Google Scholar : PubMed/NCBI
6	Quan GM and Choong PF: Anti-angiogenic therapy for osteosarcoma. Cancer Metast Rev. 25:707–713. 2006. View Article : Google Scholar
7	Dvorak HF: Vascular permeability factor/vascular endothelial growth factor: A critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 20:4368–4380. 2002. View Article : Google Scholar : PubMed/NCBI
8	Lee Y, Tokunaga T, Oshika Y, et al: Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma. Eur J Cancer. 35:1089–1093. 1999. View Article : Google Scholar : PubMed/NCBI
9	Takenaka K, Yamagishi SI, Jinnouchi Y, Nakamura K, Matsui T and Imaizumi T: Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells. Life Sci. 77:3231–3241. 2005. View Article : Google Scholar : PubMed/NCBI
10	Miller CW, Aslo A, Tsay C, et al: Frequency and structure of p53 rearrangements in human osteosarcoma. Cancer Res. 50:7950–7954. 1990.PubMed/NCBI
11	Mousses S, Mcauley L, Bell RS, Kandel R and Andrulis IL: Molecular and immunohistochemical identification of p53 alterations in bone and soft tissue sarcomas. Mod Pathol. 9:1–6. 1996.PubMed/NCBI
12	Eliseev R, Dong Y, Sampson E, et al: Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis. Oncogene. 27:3605–3614. 2008. View Article : Google Scholar : PubMed/NCBI
13	Onda M, Matsuda S, Higaki S, et al: ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer. 77:71–78. 1996. View Article : Google Scholar : PubMed/NCBI
14	Namløs HM, Meza-Zepeda LA, et al: Modulation of the osteosarcoma expression phenotype by microRNAs. PloS One. 7:e480862012. View Article : Google Scholar : PubMed/NCBI
15	Irizarry RA, Hobbs B, Collin F, et al: Exploration, normalization and summaries of high density oligonucleotide array probe level data. Biostatistics. 4:249–264. 2003. View Article : Google Scholar : PubMed/NCBI
16	Gentleman R, Carey VJ, Huber W, Irizarry RA and Dudoit S: Bioinformatics and computational biology solutions using R and Bioconductor. 746718470. Springer; New York NY: 2005, View Article : Google Scholar
17	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2008. View Article : Google Scholar
18	Harris MA, Clark J, Ireland A, et al: The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 32:D258–D261. 2004. View Article : Google Scholar
19	Lu M, Zhang Q, Deng M, et al: An analysis of human microRNA and disease associations. PloS One. 3:e34202008. View Article : Google Scholar : PubMed/NCBI
20	Franceschini A, Szklarczyk D, Frankild S, et al: STRING v9.1: Protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 41:D808–D815. 2013. View Article : Google Scholar :
21	Saito R, Smoot ME, Ono K, et al: A travel guide to Cytoscape plugins. Nat Med. 9:1069–1076. 2012.
22	Palla G, Derényi I, Farkas I and Vicsek T: Uncovering the overlapping community structure of complex networks in nature and society. Nature. 435:814–818. 2005. View Article : Google Scholar : PubMed/NCBI
23	Cui XR, Hou WR, Yang J, Hou Y and Peng ZS: Cloning and sequence analysis of ribosomal protein L8 gene (RPL8) from the (Ailuropoda melanoleuca). 2011 4th International Conference on Biomedical Engineering and Informatics; Shanghai, China. pp. 1407–1411. 2011
24	Yang J and Zhang W: New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 25:398–406. 2013. View Article : Google Scholar : PubMed/NCBI
25	Salas S, Jézéquel P, Campion L, Deville JL, Chibon F, Bartoli C, Gentet JC, Charbonnel C, Gouraud W, Voutsinos-Porche B, et al: Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2. Int J Cancer. 125:851–860. 2009. View Article : Google Scholar : PubMed/NCBI
26	Montanaro L, Mazzini G, Barbieri S, et al: Different effects of ribosome biogenesis inhibition on cell proliferation in retinoblastoma protein-and p53-deficient and proficient human osteosarcoma cell lines. Cell Prolif. 40:532–549. 2007. View Article : Google Scholar : PubMed/NCBI
27	Fukami K: Structure, regulation and function of phospholipase C isozymes. J Biochem. 131:293–299. 2002. View Article : Google Scholar : PubMed/NCBI
28	Noh DY, Kang H, Kim YC, et al: Expression of phospholipase C-gamma 1 and its transcriptional regulators in breast cancer tissues. Anticancer Res. 18:2643–2648. 1997.
29	Mamoune A, Kassis J, Kharait S, Kloeker S, Manos E, Jones DA and Wells A: DU145 human prostate carcinoma invasiveness is modulated by urokinase receptor (uPAR) downstream of epidermal growth factor receptor (EGFR) signaling. Exp Cell Res. 299:91–100. 2004. View Article : Google Scholar : PubMed/NCBI
30	Kochhar KS and Iyer AP: Hepatocyte growth factor induces activation of Nck and phospholipase C-γ in lung carcinoma cells. Cancer Lett. 104:163–169. 1996. View Article : Google Scholar : PubMed/NCBI
31	Kassis J, Radinsky R and Wells A: Motility is rate-limiting for invasion of bladder carcinoma cell lines. Int J Biochem Cell Biol. 34:762–775. 2002. View Article : Google Scholar : PubMed/NCBI
32	Zhang B, Wu Q, Ye XF, Liu S, Lin XF and Chen MC: Roles of PLC-gamma2 and PKCalpha in TPA-induced apoptosis of gastric cancer cells. World J Gastroenterol. 9:2413–2418. 2003.PubMed/NCBI
33	Dong S, Ma L, Xu N, et al: Research on the reactivation of Syk expression caused by the inhibition of DNA promoter methylation in the lung cancer. Neoplasma. 58:89–95. 2010. View Article : Google Scholar : PubMed/NCBI
34	Luo P, Yang X, Ying M, et al: Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells. Oncogene. 29:2772–2783. 2010. View Article : Google Scholar : PubMed/NCBI
35	Agoston AT, Argani P, De Marzo AM, Hicks JL and Nelson WG: Retinoblastoma pathway dysregulation causes DNA methyltrans-ferase 1 overexpression in cancer via MAD2-mediated inhibition of the anaphase-promoting complex. Am J Pathol. 170:1585–1593. 2007. View Article : Google Scholar : PubMed/NCBI
36	Yu L, Guo WC, Zhao SH, Tang J and Chen JL: Mitotic arrest defective protein 2 expression abnormality and its clinicopathologic significance in human osteosarcoma. Apmis. 118:222–229. 2010. View Article : Google Scholar : PubMed/NCBI
37	Yu L, Guo W, Zhao S, Tang J and Liu J: Knockdown of Mad2 induces osteosarcoma cell apoptosis-involved Rad21 cleavage. J Orthop Sci. 16:814–820. 2011. View Article : Google Scholar : PubMed/NCBI
38	Shichiri M, Yoshinaga K, Hisatomi H, Sugihara K and Hirata Y: Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival. Cancer Res. 62:13–17. 2002.PubMed/NCBI
39	Bischoff JR, Anderson L, Zhu Y, et al: A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 17:3052–3065. 1998. View Article : Google Scholar : PubMed/NCBI
40	Branca M, Giorgi C, Santini D, et al: Survivin as a marker of cervical intraepithelial neoplasia and high-risk human papillomavirus and a predictor of virus clearance and prognosis in cervical cancer. Am J Clin Pathol. 124:113–121. 2005. View Article : Google Scholar : PubMed/NCBI
41	Hayama S, Daigo Y, Yamabuki T, et al: Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung carcinogenesis. Cancer Res. 67:4113–4122. 2007. View Article : Google Scholar : PubMed/NCBI
42	Pickard MR, Green AR, Ellis IO, et al: Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer. Breast Cancer Res. 11:R602009. View Article : Google Scholar : PubMed/NCBI
43	Lin ML, Park JH, Nishidate T, Nakamura Y and Katagiri T: Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family. Breast Cancer Res. 9:R172007. View Article : Google Scholar : PubMed/NCBI
44	Gray D, Jubb AM, Hogue D, et al: Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers. Cancer Res. 65:9751–9761. 2005. View Article : Google Scholar : PubMed/NCBI