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Published in: Medical Oncology 3/2013

01-09-2013 | Original Paper

High SKIP expression is correlated with poor prognosis and cell proliferation of hepatocellular carcinoma

Authors: Guoliang Liu, Xiaodong Huang, Xiaopeng Cui, Jing Zhang, Lixian Wei, Runzhou Ni, Cuihua Lu

Published in: Medical Oncology | Issue 3/2013

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Abstract

Ski-interacting protein (SKIP) is a transcriptional cofactor distinct from other cofactors and involved in the regulation of many cancer-related proteins. This study investigated the expression of SKIP and its potential clinical and biological significances in hepatocellular carcinoma (HCC). Immunohistochemistry and Western blot were performed to detect the expression of SKIP in clinical HCC samples and adjacent noncancerous tissues. In addition, expression of SKIP was correlated with clinicopathological variables, and univariate and multivariate survival analyses were performed to determine the prognostic significance. Moreover, the biological significance of the aberrant expression of SKIP was investigated in vitro. High SKIP expression was detected in clinical HCC samples compared with adjacent noncancerous tissues. Expression of SKIP correlated directly with the histological grades of HCC and high expression of SKIP was associated with a poor prognosis. SKIP depletion by small interfering RNA inhibited cell proliferation and blocked S phase entry in HepG2 cells. Owing to overexpression of SKIP in HCC tissues and its important role in predicting poor prognosis and the development of HCC, SKIP could be a potential prognostic marker and therapeutic target of HCC.
Literature
1.
go back to reference El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134(6):1752–63.PubMedCrossRef El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134(6):1752–63.PubMedCrossRef
2.
go back to reference Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 2010;7(8):448–58.PubMedCrossRef Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 2010;7(8):448–58.PubMedCrossRef
4.
go back to reference Hur W, Rhim H, Jung CK, et al. SOX4 overexpression regulates the p53-mediated apoptosis in hepatocellular carcinoma: clinical implication and functional analysis in vitro. Carcinogenesis. 2010;31(7):1298–307.PubMedCrossRef Hur W, Rhim H, Jung CK, et al. SOX4 overexpression regulates the p53-mediated apoptosis in hepatocellular carcinoma: clinical implication and functional analysis in vitro. Carcinogenesis. 2010;31(7):1298–307.PubMedCrossRef
5.
go back to reference Yang H, Xiong FX, Lin M, Yang Y, Nie X, Zhou RL. LAPTM4B-35 overexpression is a risk factor for tumor recurrence and poor prognosis in hepatocellular carcinoma. J Cancer Res Clin Oncol. 2010;136(2):275–81.PubMedCrossRef Yang H, Xiong FX, Lin M, Yang Y, Nie X, Zhou RL. LAPTM4B-35 overexpression is a risk factor for tumor recurrence and poor prognosis in hepatocellular carcinoma. J Cancer Res Clin Oncol. 2010;136(2):275–81.PubMedCrossRef
6.
go back to reference Lipinski MM, Jacks T. The retinoblastoma gene family in differentiation and development. Oncogene. 1999;18:7873–82.PubMedCrossRef Lipinski MM, Jacks T. The retinoblastoma gene family in differentiation and development. Oncogene. 1999;18:7873–82.PubMedCrossRef
7.
go back to reference Harbour JW, Dean DC. Rb function in cell cycle regulation and apoptosis. Nat Cell Biol. 2000;2:E65–7.PubMedCrossRef Harbour JW, Dean DC. Rb function in cell cycle regulation and apoptosis. Nat Cell Biol. 2000;2:E65–7.PubMedCrossRef
8.
go back to reference Dahl R, Wani B, Hayman MJ. The Ski oncoprotein interacts with Skip, the human homolog of Drosophila Bx42. Oncogene. 1998;16(12):1579–86.PubMedCrossRef Dahl R, Wani B, Hayman MJ. The Ski oncoprotein interacts with Skip, the human homolog of Drosophila Bx42. Oncogene. 1998;16(12):1579–86.PubMedCrossRef
9.
go back to reference Leong GM, Subramaniam N, Figueroa J, et al. Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription. J Biol Chem. 2001;276(21):18243–8.PubMedCrossRef Leong GM, Subramaniam N, Figueroa J, et al. Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription. J Biol Chem. 2001;276(21):18243–8.PubMedCrossRef
10.
go back to reference Prathapam T, Kuhne C, Banks L. Skip interacts with the retinoblastoma tumor suppressor and inhibits its transcriptional repression activity. Nucleic Acids Res. 2002;30(23):5261–8.PubMedCrossRef Prathapam T, Kuhne C, Banks L. Skip interacts with the retinoblastoma tumor suppressor and inhibits its transcriptional repression activity. Nucleic Acids Res. 2002;30(23):5261–8.PubMedCrossRef
11.
go back to reference Folk P, Puta F, Skruzny M. Transcriptional coregulator SNW/SKIP: the concealed tie of dissimilar pathways. Cell Mol Life Sci. 2004;61(6):629–40.PubMedCrossRef Folk P, Puta F, Skruzny M. Transcriptional coregulator SNW/SKIP: the concealed tie of dissimilar pathways. Cell Mol Life Sci. 2004;61(6):629–40.PubMedCrossRef
12.
go back to reference Obama K, Kato T, Hasegawa S, Satoh S, Nakamura Y, Furukawa Y. Overexpression of peptidyl-prolyl isomerase-like 1 is associated with the growth of colon cancer cells. Clin Cancer Res. 2006;12(1):70–6.PubMedCrossRef Obama K, Kato T, Hasegawa S, Satoh S, Nakamura Y, Furukawa Y. Overexpression of peptidyl-prolyl isomerase-like 1 is associated with the growth of colon cancer cells. Clin Cancer Res. 2006;12(1):70–6.PubMedCrossRef
13.
go back to reference Xu C, Zhang J, Huang X, et al. Solution structure of human peptidyl prolyl isomerase-like protein 1 and insights into its interaction with SKIP. J Biol Chem. 2006;281(23):15900–8.PubMedCrossRef Xu C, Zhang J, Huang X, et al. Solution structure of human peptidyl prolyl isomerase-like protein 1 and insights into its interaction with SKIP. J Biol Chem. 2006;281(23):15900–8.PubMedCrossRef
14.
go back to reference Ke Q, Ji J, Cheng C, et al. Expression and prognostic role of Spy1 as a novel cell cycle protein in hepatocellular carcinoma. Exp Mol Pathol. 2009;87(3):167–72.PubMedCrossRef Ke Q, Ji J, Cheng C, et al. Expression and prognostic role of Spy1 as a novel cell cycle protein in hepatocellular carcinoma. Exp Mol Pathol. 2009;87(3):167–72.PubMedCrossRef
15.
go back to reference Xu X, Yamamoto H, Sakon M, et al. Overexpression of CDC25A phosphatase is associated with hypergrowth activity and poor prognosis of human hepatocellular carcinomas. Clin Cancer Res. 2003;9(5):1764–72.PubMed Xu X, Yamamoto H, Sakon M, et al. Overexpression of CDC25A phosphatase is associated with hypergrowth activity and poor prognosis of human hepatocellular carcinomas. Clin Cancer Res. 2003;9(5):1764–72.PubMed
16.
17.
go back to reference El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.PubMedCrossRef El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.PubMedCrossRef
18.
go back to reference Chen Y, Zhang L, Jones KA. SKIP counteracts p53-mediated apoptosis via selective regulation of p21Cip1 mRNA splicing. Genes Dev. 2011;25(7):701–16.PubMedCrossRef Chen Y, Zhang L, Jones KA. SKIP counteracts p53-mediated apoptosis via selective regulation of p21Cip1 mRNA splicing. Genes Dev. 2011;25(7):701–16.PubMedCrossRef
19.
go back to reference Kitamoto M, Nakanishi T, Kira S, et al. The assessment of proliferating cell nuclear antigen immunohistochemical staining in small hepatocellular carcinoma and its relationship to histologic characteristics and prognosis. Cancer. 1993;72(6):1859–65.PubMedCrossRef Kitamoto M, Nakanishi T, Kira S, et al. The assessment of proliferating cell nuclear antigen immunohistochemical staining in small hepatocellular carcinoma and its relationship to histologic characteristics and prognosis. Cancer. 1993;72(6):1859–65.PubMedCrossRef
20.
go back to reference Mann CD, Neal CP, Garcea G, Manson MM, Dennison AR, Berry DP. Prognostic molecular markers in hepatocellular carcinoma: a systematic review. Eur J Cancer. 2007;43(6):979–92.PubMedCrossRef Mann CD, Neal CP, Garcea G, Manson MM, Dennison AR, Berry DP. Prognostic molecular markers in hepatocellular carcinoma: a systematic review. Eur J Cancer. 2007;43(6):979–92.PubMedCrossRef
21.
go back to reference Liu S, Dong Q, Wang E. Rsf-1 overexpression correlates with poor prognosis and cell proliferation in colon cancer. Tumour Biol. 2012;33(5):1485–91.PubMedCrossRef Liu S, Dong Q, Wang E. Rsf-1 overexpression correlates with poor prognosis and cell proliferation in colon cancer. Tumour Biol. 2012;33(5):1485–91.PubMedCrossRef
22.
go back to reference Deng Q, Wang Q, Zong WY, et al. E2F8 contributes to human hepatocellular carcinoma via regulating cell proliferation. Cancer Res. 2010;70(2):782–91.PubMedCrossRef Deng Q, Wang Q, Zong WY, et al. E2F8 contributes to human hepatocellular carcinoma via regulating cell proliferation. Cancer Res. 2010;70(2):782–91.PubMedCrossRef
23.
go back to reference Emori TK, Kitamura K, Okazaki K. Nuclear Smad7 overexpressed in mesenchymal cells acts as a transcriptional corepressor by interacting with HDAC-1 and E2F to regulate cell cycle. Biol Open. 2012;1(3):247–60.PubMedCrossRef Emori TK, Kitamura K, Okazaki K. Nuclear Smad7 overexpressed in mesenchymal cells acts as a transcriptional corepressor by interacting with HDAC-1 and E2F to regulate cell cycle. Biol Open. 2012;1(3):247–60.PubMedCrossRef
24.
go back to reference Han Y, He H, Peng F, et al. SKLB70326, a novel small-molecule inhibitor of cell-cycle progression, induces G(0)/G(1) phase arrest and apoptosis in human hepatic carcinoma cells. Biochem Biophys Res Commun. 2012;421(4):684–9.PubMedCrossRef Han Y, He H, Peng F, et al. SKLB70326, a novel small-molecule inhibitor of cell-cycle progression, induces G(0)/G(1) phase arrest and apoptosis in human hepatic carcinoma cells. Biochem Biophys Res Commun. 2012;421(4):684–9.PubMedCrossRef
25.
go back to reference Muller H, Helin K. The E2F transcription factors: key regulators of cell proliferation. Biochim Biophys Acta. 2000;1470:M1–12.PubMed Muller H, Helin K. The E2F transcription factors: key regulators of cell proliferation. Biochim Biophys Acta. 2000;1470:M1–12.PubMed
26.
go back to reference Lu ZL, Luo DZ, Wen JM. Expression and significance of tumor-related genes in HCC. World J Gastroenterol. 2005;11:3850–4.PubMed Lu ZL, Luo DZ, Wen JM. Expression and significance of tumor-related genes in HCC. World J Gastroenterol. 2005;11:3850–4.PubMed
Metadata
Title
High SKIP expression is correlated with poor prognosis and cell proliferation of hepatocellular carcinoma
Authors
Guoliang Liu
Xiaodong Huang
Xiaopeng Cui
Jing Zhang
Lixian Wei
Runzhou Ni
Cuihua Lu
Publication date
01-09-2013
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2013
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0537-4

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