OY-TES-1 may regulate the malignant behavior of liver cancer via NANOG, CD9, CCND2 and CDCA3: A bioinformatic analysis 
combine with RNAi and oligonucleotide microarray

Hu,Qiping; Fu,Jun; Luo,Bin; Huang,Miao; Guo,Wenwen; Lin,Yongda; Xie,Xiaoxun; Xiao,Shaowen

doi:10.3892/or.2015.3792

OY-TES-1 may regulate the malignant behavior of liver cancer via NANOG, CD9, CCND2 and CDCA3: A bioinformatic analysis combine with RNAi and oligonucleotide microarray

Authors:
- Qiping Hu
- Jun Fu
- Bin Luo
- Miao Huang
- Wenwen Guo
- Yongda Lin
- Xiaoxun Xie
- Shaowen Xiao
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Affiliations: Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Radiology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Neurosurgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: February 10, 2015 https://doi.org/10.3892/or.2015.3792
Pages: 1965-1975

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Abstract

Given its tumor-specific expression, including liver cancer, OY-TES-1 is a potential molecular marker for the diagnosis and immunotherapy of liver cancers. However, investigations of the mechanisms and the role of OY-TES-1 in liver cancer are rare. In the present study, based on a comprehensive bioinformatic analysis combined with RNA interference (RNAi) and oligonucleotide microarray, we report for the first time that downregulation of OY-TES-1 resulted in significant changes in expression of NANOG, CD9, CCND2 and CDCA3 in the liver cancer cell line BEL-7404. NANOG, CD9, CCND2 and CDCA3 may be involved in cell proliferation, migration, invasion and apoptosis, yet also may be functionally related to each other and OY-TES-1. Among these molecules, we identified that NANOG, containing a Kazal-2 binding motif and homeobox, may be the most likely candidate protein interacting with OY-TES-1 in liver cancer. Thus, the present study may provide important information for further investigation of the roles of OY-TES-1 in liver cancer.

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1	Mo QG, Liang AM, Yang NW, et al: Surgery-predominant comprehensive therapy for 134 patients with small hepatocellular carcinoma. Ai Zheng. 22:189–191. 2003.(In Chinese). PubMed/NCBI
2	Yoon H, Lee H, Kim HJ, et al: Tudor domain-containing protein 4 as a potential cancer/testis antigen in liver cancer. Tohoku J Exp Med. 224:41–46. 2011. View Article : Google Scholar : PubMed/NCBI
3	Song MH, Choi KU, Shin DH, et al: Identification of the cancer/testis antigens AKAP3 and CTp11 by SEREX in hepatocellular carcinoma. Oncol Rep. 28:1792–1798. 2012.PubMed/NCBI
4	Xing Q, Pang XW, Peng JR, et al: Identification of new cytotoxic T-lymphocyte epitopes from cancer testis antigen HCA587. Biochem Biophys Res Commun. 372:331–335. 2008. View Article : Google Scholar : PubMed/NCBI
5	Zhao L, Mou DC, Leng XS, et al: Expression of cancer-testis antigens in hepatocellular carcinoma. World J Gastroenterol. 10:2034–2038. 2004.PubMed/NCBI
6	Pang PH, Chan KT, Tse LY, et al: Induction of cytotoxic T cell response against HCA661 positive cancer cells through activation with novel HLA-A*0201 restricted epitopes. Cancer Lett. 256:178–185. 2007. View Article : Google Scholar : PubMed/NCBI
7	Yang XA, Dong XY, Qiao H, et al: Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues. Lab Invest. 85:205–213. 2005. View Article : Google Scholar
8	Yin YH, Li YY, Qiao H, et al: TSPY is a cancer testis antigen expressed in human hepatocellular carcinoma. Br J Cancer. 93:458–463. 2005. View Article : Google Scholar : PubMed/NCBI
9	Ono T, Kurashige T, Harada N, et al: Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen. Proc Natl Acad Sci USA. 98:3282–3287. 2001. View Article : Google Scholar : PubMed/NCBI
10	Fan R, Huang W, Xiao SW, et al: OY-TES-1 expression and serum immunoreactivity in hepatocellular carcinoma. World Chi J Digest. 17:3307–3312. 2009.(In Chinese).
11	Tammela J, Uenaka A, Ono T, et al: OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer. Int J Oncol. 29:903–910. 2006.PubMed/NCBI
12	Whitehurst AW, Xie Y, Purinton SC, et al: Tumor antigen acrosin binding protein normalizes mitotic spindle function to promote cancer cell proliferation. Cancer Res. 70:7652–7661. 2010. View Article : Google Scholar : PubMed/NCBI
13	Kanemori Y, Ryu JH, Sudo M, et al: Two functional forms of ACRBP/sp32 are produced by pre-mRNA alternative splicing in the mouse. Biol Reprod. 88:1052013. View Article : Google Scholar : PubMed/NCBI
14	Okumura H, Noguchi Y, Uenaka A, et al: Identification of an HLA-A24-restricted OY-TES-1 epitope recognized by cytotoxic T-cells. Microbiol Immunol. 49:1009–1016. 2005. View Article : Google Scholar : PubMed/NCBI
15	Cen YH, Guo WW, Luo B, et al: Knockdown of OY-TES-1 by RNAi causes cell cycle arrest and migration decrease in bone marrow-derived mesenchymal stem cells. Cell Biol Int. 36:917–922. 2012. View Article : Google Scholar : PubMed/NCBI
16	Yellaboina S, Tasneem A, Zaykin DV, et al: DOMINE: a comprehensive collection of known and predicted domain-domain interactions. Nucleic Acids Res. 39:D730–D735. 2011. View Article : Google Scholar :
17	Finn RD, Bateman A, Clements J, et al: Pfam: the protein families database. Nucleic Acids Res. 42:D222–D230. 2014. View Article : Google Scholar :
18	Kumar B, Sharma D, Sharma P, et al: Proteomic analysis of Mycobacterium tuberculosis isolates resistant to kanamycin and amikacin. J Proteomics. 94:68–77. 2013. View Article : Google Scholar : PubMed/NCBI
19	Rhodes DR, Kalyana-Sundaram S, Mahavisno V, et al: Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 9:166–180. 2007. View Article : Google Scholar : PubMed/NCBI
20	Wilson BJ and Giguère V: Identification of novel pathway partners of p68 and p72 RNA helicases through Oncomine meta-analysis. BMC Genomics. 8:4192007. View Article : Google Scholar : PubMed/NCBI
21	Li Z, Ma B, Lu M, et al: Construction of network for protein kinases that play a role in acute pancreatitis. Pancreas. 42:607–613. 2013. View Article : Google Scholar
22	Melaiu O, Cristaudo A, Melissari E, et al: A review of transcriptome studies combined with data mining reveals novel potential markers of malignant pleural mesothelioma. Mutat Res. 750:132–140. 2012. View Article : Google Scholar
23	Smith IM, Glazer CA, Mithani SK, et al: Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer. PLoS One. 4:e49612009. View Article : Google Scholar : PubMed/NCBI
24	Suyama T, Shiraishi T, Zeng Y, et al: Expression of cancer/testis antigens in prostate cancer is associated with disease progression. Prostate. 70:1778–1787. 2010.PubMed/NCBI
25	Warde-Farley D, Donaldson SL, Comes O, et al: The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 38:W214–W220. 2010. View Article : Google Scholar : PubMed/NCBI
26	Williamson MP, Marion D and Wüthrich K: Secondary structure in the solution conformation of the proteinase inhibitor IIA from bull seminal plasma by nuclear magnetic resonance. J Mol Biol. 173:341–359. 1984. View Article : Google Scholar : PubMed/NCBI
27	Laskowski M Jr, Kato I, Ardelt W, et al: Ovomucoid third domains from 100 avian species: isolation, sequences, and hypervariability of enzyme-inhibitor contact residues. Biochemistry. 26:202–221. 1987. View Article : Google Scholar : PubMed/NCBI
28	Schlott B, Wöhnert J, Icke C, et al: Interaction of Kazal-type inhibitor domains with serine proteinases: biochemical and structural studies. J Mol Biol. 318:533–546. 2002. View Article : Google Scholar : PubMed/NCBI
29	Funk JD, Nedialkov YA, Xu D and Burton ZF: A key role for the α1 helix of human RAP74 in the initiation and elongation of RNA chains. J Biol Chem. 277:46998–47003. 2002. View Article : Google Scholar : PubMed/NCBI
30	Baba T, Niida Y, Michikawa Y, et al: An acrosomal protein, sp32, in mammalian sperm is a binding protein specific for two proacrosins and an acrosin intermediate. J Biol Chem. 269:10133–10140. 1994.PubMed/NCBI
31	Hase H, Kanno Y, Kojima H, et al: CD27 and CD40 inhibit p53-independent mitochondrial pathways in apoptosis of B cells induced by B cell receptor ligation. J Biol Chem. 277:46950–46958. 2002. View Article : Google Scholar : PubMed/NCBI
32	Shi JY, Gao Q, Wang ZC, et al: Margin-infiltrating CD20⁺ B cells display an atypical memory phenotype and correlate with favorable prognosis in hepatocellular carcinoma. Clin Cancer Res. 19:5994–6005. 2013. View Article : Google Scholar : PubMed/NCBI
33	Wang XD, Wang L, Ji FJ, et al: Decreased CD27 on B lymphocytes in patients with primary hepatocellular carcinoma. J Int Med Res. 40:307–316. 2012. View Article : Google Scholar : PubMed/NCBI
34	Yang ZQ, Yang ZY, Zhang LD, et al: Increased liver-infiltrating CD8⁺FoxP3⁺ regulatory T cells are associated with tumor stage in hepatocellular carcinoma patients. Hum Immunol. 71:1180–1186. 2010. View Article : Google Scholar : PubMed/NCBI
35	Zhang X, Xu LS, Wang ZQ, et al: ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells. FEBS Lett. 570:7–12. 2004. View Article : Google Scholar : PubMed/NCBI
36	Doyon Y, Cayrou C, Ullah M, et al: ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 21:51–64. 2006. View Article : Google Scholar : PubMed/NCBI
37	Li X, Cai L, Chen H, et al: Inhibitor of growth 4 induces growth suppression and apoptosis in glioma U87MG. Pathobiology. 76:181–192. 2009. View Article : Google Scholar : PubMed/NCBI
38	Karabulut B, Karaca B, Atmaca H, et al: Regulation of apoptosis-related molecules by synergistic combination of all-trans retinoic acid and zoledronic acid in hormone-refractory prostate cancer cell lines. Mol Biol Rep. 38:249–259. 2011. View Article : Google Scholar
39	Matsuda A, Suzuki Y, Honda G, et al: Large-scale identification and characterization of human genes that activate NF-κB and MAPK signaling pathways. Oncogene. 22:3307–3318. 2003. View Article : Google Scholar : PubMed/NCBI
40	Masellis-Smith A and Shaw AR: CD9-regulated adhesion. Anti-CD9 monoclonal antibody induces pre-B cell adhesion to bone marrow fibroblasts through de novo recognition of fibronectin. J Immunol. 152:2768–2777. 1994.PubMed/NCBI
41	Leung KT, Chan KY, Ng PC, et al: The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34⁺ hematopoietic stem and progenitor cells. Blood. 117:1840–1850. 2011. View Article : Google Scholar
42	Powner D, Kopp PM, Monkley SJ, et al: Tetraspanin CD9 in cell migration. Biochem Soc Trans. 39:563–567. 2011. View Article : Google Scholar : PubMed/NCBI
43	Kanetaka K, Sakamoto M, Yamamoto Y, et al: Overexpression of tetraspanin CO-029 in hepatocellular carcinoma. J Hepatol. 35:637–642. 2001. View Article : Google Scholar : PubMed/NCBI
44	Li J and Li G: Cell cycle regulator ING4 is a suppressor of melanoma angiogenesis that is regulated by the metastasis suppressor BRMS1. Cancer Res. 70:10445–10453. 2010. View Article : Google Scholar : PubMed/NCBI
45	Meyerson M and Harlow E: Identification of G₁ kinase activity for cdk6, a novel cyclin D partner. Mol Cell Biol. 14:2077–2086. 1994.PubMed/NCBI
46	Yadav S, Pandey A, Shukla A, et al: miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2. J Biol Chem. 286:37347–37357. 2011. View Article : Google Scholar : PubMed/NCBI
47	Zhou J, Tian Y, Li J, et al: miR-206 is down-regulated in breast cancer and inhibits cell proliferation through the up-regulation of cyclinD2. Biochem Biophys Res Commun. 433:207–212. 2013. View Article : Google Scholar : PubMed/NCBI
48	Zhang L, Liu X, Jin H, et al: miR-206 inhibits gastric cancer proliferation in part by repressing cyclinD2. Cancer Lett. 332:94–101. 2013. View Article : Google Scholar : PubMed/NCBI
49	Chen BB, Glasser JR, Coon TA, et al: F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation. Blood. 119:3132–3141. 2012. View Article : Google Scholar : PubMed/NCBI
50	Igawa T, Sato Y, Takata K, et al: Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma. Cancer Sci. 102:2103–2107. 2011. View Article : Google Scholar : PubMed/NCBI
51	Dong Q, Meng P, Wang T, et al: MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 5:e101472010. View Article : Google Scholar : PubMed/NCBI
52	Darr H, Mayshar Y and Benvenisty N: Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. 133:1193–1201. 2006. View Article : Google Scholar : PubMed/NCBI
53	Yang L, Zhang X, Zhang M, et al: Increased Nanog expression promotes tumor development and cisplatin resistance in human esophageal cancer cells. Cell Physiol Biochem. 30:943–952. 2012. View Article : Google Scholar : PubMed/NCBI
54	Siu MK, Wong ES, Kong DS, et al: Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers. Oncogene. 32:3500–3509. 2013. View Article : Google Scholar
55	Valdez BC, Perlaky L, Saijo Y, et al: A region of antisense RNA from human p120 cDNA with high homology to mouse p120 cDNA inhibits NIH 3T3 proliferation. Cancer Res. 152:5681–5686. 1992.
56	Siggers RH and Hackam DJ: The role of innate immune-stimulated epithelial apoptosis during gastrointestinal inflammatory diseases. Cell Mol Life Sci. 68:3623–3634. 2011. View Article : Google Scholar : PubMed/NCBI
57	Sharan R, Ulitsky I and Shamir R: Network-based prediction of protein function. Mol Syst Biol. 3:882007. View Article : Google Scholar : PubMed/NCBI
58	Dodurga Y, Oymak Y, Gündüz C, et al: Leukemogenesis as a new approach to investigate the correlation between up regulated gene 4/upregulator of cell proliferation (URG4/URGCP) and signal transduction genes in leukemia. Mol Biol Rep. 40:3043–3048. 2013. View Article : Google Scholar
59	Faussillon M, Monnier L, Junien C and Jeanpierre C: Frequent overexpression of cyclin D2/cyclin-dependent kinase 4 in Wilms’ tumor. Cancer Lett. 221:67–75. 2005. View Article : Google Scholar : PubMed/NCBI
60	Park TJ, Chun JY, Bae JS, et al: CCND2 polymorphisms associated with clearance of HBV infection. J Hum Genet. 55:416–420. 2010. View Article : Google Scholar : PubMed/NCBI
61	Takano Y, Kato Y, van Diest PJ, et al: Cyclin D2 overexpression and lack of p27 correlate positively and cyclin E inversely with a poor prognosis in gastric cancer cases. Am J Pathol. 156:585–594. 2000. View Article : Google Scholar : PubMed/NCBI
62	Uchida F, Uzawa K, Kasamatsu A, et al: Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest. BMC Cancer. 12:3212012. View Article : Google Scholar : PubMed/NCBI
63	Chen J, Zhu S, Jiang N, et al: HoxB3 promotes prostate cancer cell progression by transactivating CDCA3. Cancer Lett. 330:217–224. 2013. View Article : Google Scholar
64	Bunt J, de Haas TG, Hasselt NE, et al: Regulation of cell cycle genes and induction of senescence by overexpression of OTX2 in medulloblastoma cell lines. Mol Cancer Res. 8:1344–1357. 2010. View Article : Google Scholar : PubMed/NCBI
65	Visconti R, Palazzo L, Della Monica R and Grieco D: Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit. Nat Commun. 3:8942012. View Article : Google Scholar : PubMed/NCBI
66	Funakoshi T, Tachibana I, Hoshida Y, et al: Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer. Oncogene. 22:674–687. 2003. View Article : Google Scholar : PubMed/NCBI
67	Ovalle S, Gutiérrez-López MD, Olmo N, et al: The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells. Int J Cancer. 121:2140–2152. 2007. View Article : Google Scholar : PubMed/NCBI
68	Saito Y, Tachibana I, Takeda Y, et al: Absence of CD9 enhances adhesion-dependent morphologic differentiation, survival, and matrix metalloproteinase-2 production in small cell lung cancer cells. Cancer Res. 66:9557–9565. 2006. View Article : Google Scholar : PubMed/NCBI
69	Murayama Y, Miyagawa J, Oritani K, et al: CD9-mediated activation of the p46 Shc isoform leads to apoptosis in cancer cells. J Cell Sci. 117:3379–3388. 2004. View Article : Google Scholar : PubMed/NCBI
70	Zheng R, Yano S, Zhang H, et al: CD9 overexpression suppressed the liver metastasis and malignant ascites via inhibition of proliferation and motility of small-cell lung cancer cells in NK cell-depleted SCID mice. Oncol Res. 15:365–372. 2005.
71	Kim JS, Kim J, Kim BS, et al: Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog. Exp Mol Med. 37:601–607. 2005. View Article : Google Scholar
72	Oh JH, Do HJ, Yang HM, et al: Identification of a putative trans-activation domain in human Nanog. Exp Mol Med. 37:250–254. 2005. View Article : Google Scholar : PubMed/NCBI
73	Shan J, Shen J, Liu L, et al: Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology. 56:1004–1014. 2012. View Article : Google Scholar : PubMed/NCBI
74	Sun C, Sun L, Jiang K, et al: NANOG promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL/SMAD3 signaling pathway. Int J Biochem Cell Biol. 45:1099–1108. 2013. View Article : Google Scholar : PubMed/NCBI
75	Du Y, Shi L, Wang T, Liu Z and Wang Z: Nanog siRNA plus Cisplatin may enhance the sensitivity of chemotherapy in esophageal cancer. J Cancer Res Clin Oncol. 138:1759–1767. 2012. View Article : Google Scholar : PubMed/NCBI
76	Ji W and Jiang Z: Effect of shRNA-mediated inhibition of Nanog gene expression on the behavior of human gastric cancer cells. Oncol Lett. 6:367–374. 2013.PubMed/NCBI
77	Yu J, Zhang SS, Saito K, et al: PTEN regulation by Akt-EGR1-ARF-PTEN axis. EMBO J. 28:21–33. 2009. View Article : Google Scholar :