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Published in: Tumor Biology 6/2014

01-06-2014 | Research Article

SUZ12 is involved in progression of non-small cell lung cancer by promoting cell proliferation and metastasis

Authors: Chunhua Liu, Xuefei Shi, Li Wang, Ying Wu, Feiyan Jin, Cuiqing Bai, Yong Song

Published in: Tumor Biology | Issue 6/2014

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Abstract

The suppressor of zeste-12 protein (SUZ12), a core component of Polycomb repressive complex 2 (PRC2), is implicated in transcriptional silencing by generating di- and tri-methylation of lysine 27 on histone H3 (H3K27Me3). Although SUZ12 is known to be of great importance in several human cancer tumorigenesis, limited data are available on the expression profile and functional role of SUZ12 in non-small cell lung cancer (NSCLC). Here, we determined the expression level of SUZ12 in 40 paired clinical NSCLC tissues and adjacent normal tissues by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The results showed that SUZ12 was anomalously expressed in NSCLC tissues compared to adjacent noncancerous tissues (P < 0.05) and was highly correlated to tumor size, lymph node metastasis, and clinical stages (P < 0.05). Additionally, siRNA-mediated knockdown of SUZ12 could inhibit tumor cell growth, migration, and invasion, indicating that SUZ12 might function as an oncogene in NSCLC initiation and progression. Furthermore, we found that SUZ12 silencing significantly reduced the expression levels of transcription factor transcription factor E2F1 (E2F1) as well as potential metastasis promoters Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) and roundabout homolog 1 (ROBO1) through Western blot analysis. Altogether, we provide evidences suggesting that SUZ12 is an oncogene in NSCLC and can regulate NSCLC cells proliferation and metastasis partly via reducing E2F1, ROCK1, and ROBO1. Thus, SUZ12 may represent a new potential diagnostic marker for NSCLC and may be a novel therapeutic target for NSCLC intervention.
Literature
5.
go back to reference Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M. Non-small cell lung cancer—genetic predictors. Biomed Pap Med Fac Univ Palacky Olomouc Czechoslovakia. 2013;157(2):125–36. doi:10.5507/bp.2013.034. Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M. Non-small cell lung cancer—genetic predictors. Biomed Pap Med Fac Univ Palacky Olomouc Czechoslovakia. 2013;157(2):125–36. doi:10.​5507/​bp.​2013.​034.
7.
go back to reference Zhou Q, Zhang XC, Chen ZH, Yin XL, Yang JJ, Xu CR, et al. Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(24):3316–21. doi:10.1200/jco.2010.33.3757.CrossRef Zhou Q, Zhang XC, Chen ZH, Yin XL, Yang JJ, Xu CR, et al. Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(24):3316–21. doi:10.​1200/​jco.​2010.​33.​3757.CrossRef
8.
go back to reference Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature. 2006;441(7091):349–53. doi:10.1038/nature04733.CrossRefPubMed Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature. 2006;441(7091):349–53. doi:10.​1038/​nature04733.CrossRefPubMed
9.
go back to reference Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science (New York, NY). 2002;298(5595):1039–43. doi:10.1126/science.1076997.CrossRef Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science (New York, NY). 2002;298(5595):1039–43. doi:10.​1126/​science.​1076997.CrossRef
10.
16.
go back to reference Bachmann IM, Halvorsen OJ, Collett K, Stefansson IM, Straume O, Haukaas SA, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(2):268–73. doi:10.1200/jco.2005.01.5180.CrossRef Bachmann IM, Halvorsen OJ, Collett K, Stefansson IM, Straume O, Haukaas SA, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(2):268–73. doi:10.​1200/​jco.​2005.​01.​5180.CrossRef
19.
go back to reference Saramaki OR, Tammela TL, Martikainen PM, Vessella RL, Visakorpi T. The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer. Genes Chromosom Cancer. 2006;45(7):639–45. doi:10.1002/gcc.20327.CrossRefPubMed Saramaki OR, Tammela TL, Martikainen PM, Vessella RL, Visakorpi T. The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer. Genes Chromosom Cancer. 2006;45(7):639–45. doi:10.​1002/​gcc.​20327.CrossRefPubMed
20.
go back to reference Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–9. doi:10.1038/nature01075.CrossRefPubMed Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–9. doi:10.​1038/​nature01075.CrossRefPubMed
24.
go back to reference Saito M, Helin K, Valentine MB, Griffith BB, Willman CL, Harlow E, et al. Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line. Genomics. 1995;25(1):130–8.CrossRefPubMed Saito M, Helin K, Valentine MB, Griffith BB, Willman CL, Harlow E, et al. Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line. Genomics. 1995;25(1):130–8.CrossRefPubMed
25.
go back to reference Suzuki T, Yasui W, Yokozaki H, Naka K, Ishikawa T, Tahara E. Expression of the E2F family in human gastrointestinal carcinomas. Int J Cancer. 1999;81(4):535–8.CrossRefPubMed Suzuki T, Yasui W, Yokozaki H, Naka K, Ishikawa T, Tahara E. Expression of the E2F family in human gastrointestinal carcinomas. Int J Cancer. 1999;81(4):535–8.CrossRefPubMed
26.
go back to reference Zhang SY, Liu SC, Al-Saleem LF, Holloran D, Babb J, Guo X, et al. E2F-1: a proliferative marker of breast neoplasia. Cancer Epidemiol Biomarkers Prev. 2000;9(4):395–401.PubMed Zhang SY, Liu SC, Al-Saleem LF, Holloran D, Babb J, Guo X, et al. E2F-1: a proliferative marker of breast neoplasia. Cancer Epidemiol Biomarkers Prev. 2000;9(4):395–401.PubMed
28.
go back to reference Evangelou K, Kotsinas A, Mariolis-Sapsakos T, Giannopoulos A, Tsantoulis PK, Constantinides C, et al. E2F-1 overexpression correlates with decreased proliferation and better prognosis in adenocarcinomas of Barrett oesophagus. J Clin Pathol. 2008;61(5):601–5. doi:10.1136/jcp.2007.050963.CrossRefPubMed Evangelou K, Kotsinas A, Mariolis-Sapsakos T, Giannopoulos A, Tsantoulis PK, Constantinides C, et al. E2F-1 overexpression correlates with decreased proliferation and better prognosis in adenocarcinomas of Barrett oesophagus. J Clin Pathol. 2008;61(5):601–5. doi:10.​1136/​jcp.​2007.​050963.CrossRefPubMed
29.
go back to reference Kwong RA, Nguyen TV, Bova RJ, Kench JG, Cole IE, Musgrove EA, et al. Overexpression of E2F-1 is associated with increased disease-free survival in squamous cell carcinoma of the anterior tongue. Clin Cancer Res Off J Am Assoc Cancer Res. 2003;9(10 Pt 1):3705–11. Kwong RA, Nguyen TV, Bova RJ, Kench JG, Cole IE, Musgrove EA, et al. Overexpression of E2F-1 is associated with increased disease-free survival in squamous cell carcinoma of the anterior tongue. Clin Cancer Res Off J Am Assoc Cancer Res. 2003;9(10 Pt 1):3705–11.
30.
go back to reference Lee J, Park CK, Park JO, Lim T, Park YS, Lim HY, et al. Impact of E2F-1 expression on clinical outcome of gastric adenocarcinoma patients with adjuvant chemoradiation therapy. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14(1):82–8. doi:10.1158/1078-0432.ccr-07-0612.CrossRef Lee J, Park CK, Park JO, Lim T, Park YS, Lim HY, et al. Impact of E2F-1 expression on clinical outcome of gastric adenocarcinoma patients with adjuvant chemoradiation therapy. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14(1):82–8. doi:10.​1158/​1078-0432.​ccr-07-0612.CrossRef
31.
go back to reference Moller MB, Kania PW, Ino Y, Gerdes AM, Nielsen O, Louis DN, et al. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma: prognostic significance of E2F-1 and p16INK4A. Leukemia. 2000;14(5):898–904.CrossRefPubMed Moller MB, Kania PW, Ino Y, Gerdes AM, Nielsen O, Louis DN, et al. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma: prognostic significance of E2F-1 and p16INK4A. Leukemia. 2000;14(5):898–904.CrossRefPubMed
32.
go back to reference Rabbani F, Richon VM, Orlow I, Lu ML, Drobnjak M, Dudas M, et al. Prognostic significance of transcription factor E2F-1 in bladder cancer: genotypic and phenotypic characterization. J Natl Cancer Inst. 1999;91(10):874–81.CrossRefPubMed Rabbani F, Richon VM, Orlow I, Lu ML, Drobnjak M, Dudas M, et al. Prognostic significance of transcription factor E2F-1 in bladder cancer: genotypic and phenotypic characterization. J Natl Cancer Inst. 1999;91(10):874–81.CrossRefPubMed
33.
go back to reference Saiz AD, Olvera M, Rezk S, Florentine BA, McCourty A, Brynes RK. Immunohistochemical expression of cyclin D1, E2F-1, and Ki-67 in benign and malignant thyroid lesions. J Pathol. 2002;198(2):157–62. doi:10.1002/path.1185.CrossRefPubMed Saiz AD, Olvera M, Rezk S, Florentine BA, McCourty A, Brynes RK. Immunohistochemical expression of cyclin D1, E2F-1, and Ki-67 in benign and malignant thyroid lesions. J Pathol. 2002;198(2):157–62. doi:10.​1002/​path.​1185.CrossRefPubMed
34.
go back to reference Huang CL, Liu D, Nakano J, Yokomise H, Ueno M, Kadota K, et al. E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2007;13(23):6938–46. doi:10.1158/1078-0432.ccr-07-1539.CrossRef Huang CL, Liu D, Nakano J, Yokomise H, Ueno M, Kadota K, et al. E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2007;13(23):6938–46. doi:10.​1158/​1078-0432.​ccr-07-1539.CrossRef
38.
go back to reference Zhang C, Zhang S, Zhang Z, He J, Xu Y, Liu S. ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc. Oncogene. 2013. doi:10.1038/onc.2013.505. Zhang C, Zhang S, Zhang Z, He J, Xu Y, Liu S. ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc. Oncogene. 2013. doi:10.​1038/​onc.​2013.​505.
40.
go back to reference Lane J, Martin TA, Watkins G, Mansel RE, Jiang WG. The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer. Int J Oncol. 2008;33(3):585–93.PubMed Lane J, Martin TA, Watkins G, Mansel RE, Jiang WG. The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer. Int J Oncol. 2008;33(3):585–93.PubMed
45.
go back to reference Guan H, Zu G, Xie Y, Tang H, Johnson M, Xu X, et al. Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses. J Immunol (Baltimore, Md : 1950). 2003;171(12):6519–26.CrossRef Guan H, Zu G, Xie Y, Tang H, Johnson M, Xu X, et al. Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses. J Immunol (Baltimore, Md : 1950). 2003;171(12):6519–26.CrossRef
48.
go back to reference Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, Goodman CS, et al. Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell. 1998;92(2):205–15.CrossRefPubMed Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, Goodman CS, et al. Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell. 1998;92(2):205–15.CrossRefPubMed
49.
go back to reference Singh RK, Indra D, Mitra S, Mondal RK, Basu PS, Roy A, et al. Deletions in chromosome 4 differentially associated with the development of cervical cancer: evidence of slit2 as a candidate tumor suppressor gene. Hum Genet. 2007;122(1):71–81. doi:10.1007/s00439-007-0375-6.CrossRefPubMed Singh RK, Indra D, Mitra S, Mondal RK, Basu PS, Roy A, et al. Deletions in chromosome 4 differentially associated with the development of cervical cancer: evidence of slit2 as a candidate tumor suppressor gene. Hum Genet. 2007;122(1):71–81. doi:10.​1007/​s00439-007-0375-6.CrossRefPubMed
Metadata
Title
SUZ12 is involved in progression of non-small cell lung cancer by promoting cell proliferation and metastasis
Authors
Chunhua Liu
Xuefei Shi
Li Wang
Ying Wu
Feiyan Jin
Cuiqing Bai
Yong Song
Publication date
01-06-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-1804-5

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