Skip to main content
Erschienen in: Medical Oncology 6/2014

01.06.2014 | Original Paper

Clinicopathological significance of SIRT1 expression in colorectal adenocarcinoma

verfasst von: Liang Lv, Zhanlong Shen, Jizhun Zhang, Hui Zhang, Jianqiang Dong, Yichao Yan, Fangfang Liu, Kewei Jiang, Yingjiang Ye, Shan Wang

Erschienen in: Medical Oncology | Ausgabe 6/2014

Einloggen, um Zugang zu erhalten

Abstract

Sirtuin 1 (SIRT1) has been reported to have diverse roles in various biological processes through deacetylation of histone and nonhistone proteins. However, the correlations between SIRT1 protein expression, clinicopathological parameters, and survival of colorectal cancer patients remain unclear. SIRT1 protein expression in a paraffin-embedded tissue microarray, including 13 benign adenomas, nine liver metastasis tissues, and 120 paired colorectal cancer and normal mucosa tissues, was measured by immunohistochemistry. SIRT1 mRNA and protein expression in colon cancer cell lines with different metastatic potential and normal colon cells were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The correlations between SIRT1 protein expression, clinicopathological features, and prognosis were analyzed. All samples (100 %) were positive for SIRT1, with variable staining in the cytoplasm rather than the nucleus. There was significant difference in SIRT1 overexpression between adenocarcinomas and normal mucosal tissues (P < 0.01, χ 2 test). SIRT1 overexpression was more frequently observed in advanced-stage tumors and lymph node or liver metastases (P = 0.046, 0.002, and 0.004, respectively, χ 2 test). SIRT1 expression was also significantly elevated in the more aggressive colon cancer cell line SW620. SIRT1 overexpression was significantly correlated with poor overall survival (P = 0.013, log-rank test) and disease-free survival (P = 0.012, log-rank test). SIRT1 overexpression was correlated with advanced-stage and poor prognosis. SIRT1 may play an important role in the progression of colorectal cancer.
Literatur
1.
Zurück zum Zitat Guarente L, Franklin H. Epstein lecture: sirtuins, aging, and medicine. N Engl J Med. 2011;364:2235–44.PubMedCrossRef Guarente L, Franklin H. Epstein lecture: sirtuins, aging, and medicine. N Engl J Med. 2011;364:2235–44.PubMedCrossRef
2.
Zurück zum Zitat Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225–38.PubMed Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225–38.PubMed
3.
Zurück zum Zitat Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004;305:390–2.PubMedCrossRef Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004;305:390–2.PubMedCrossRef
4.
Zurück zum Zitat Boily G, Seifert EL, Bevilacqua L, He XH, Sabourin G, Estey C, et al. SirT1 regulates energy metabolism and response to caloric restriction in mice. PLoS One. 2008;3:e1759.PubMedCentralPubMedCrossRef Boily G, Seifert EL, Bevilacqua L, He XH, Sabourin G, Estey C, et al. SirT1 regulates energy metabolism and response to caloric restriction in mice. PLoS One. 2008;3:e1759.PubMedCentralPubMedCrossRef
5.
Zurück zum Zitat Kundu JK, Surh YJ. Emerging avenues linking inflammation and cancer. Free Radic Biol Med. 2012;52:2013–37.PubMedCrossRef Kundu JK, Surh YJ. Emerging avenues linking inflammation and cancer. Free Radic Biol Med. 2012;52:2013–37.PubMedCrossRef
6.
Zurück zum Zitat Zhu X, Liu Q, Wang M, Liang M, Yang X, Xu X, et al. Activation of Sirt1 by resveratrol inhibits TNF-alpha induced inflammation in fibroblasts. PLoS One. 2011;6:e27081.PubMedCentralPubMedCrossRef Zhu X, Liu Q, Wang M, Liang M, Yang X, Xu X, et al. Activation of Sirt1 by resveratrol inhibits TNF-alpha induced inflammation in fibroblasts. PLoS One. 2011;6:e27081.PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Zhang Z, Lowry SF, Guarente L, Haimovich B. Roles of SIRT1 in the acute and restorative phases following induction of inflammation. J Biol Chem. 2010;285:41391–401.PubMedCentralPubMedCrossRef Zhang Z, Lowry SF, Guarente L, Haimovich B. Roles of SIRT1 in the acute and restorative phases following induction of inflammation. J Biol Chem. 2010;285:41391–401.PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Ming M, Shea CR, Guo X, Li X, Soltani K, Han W, et al. Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C. Proc Natl Acad Sci USA. 2010;107:22623–8.PubMedCentralPubMedCrossRef Ming M, Shea CR, Guo X, Li X, Soltani K, Han W, et al. Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C. Proc Natl Acad Sci USA. 2010;107:22623–8.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Zhang Y, Zhang M, Dong H, Yong S, Li X, Olashaw N, et al. Deacetylation of cortactin by SIRT1 promotes cell migration. Oncogene. 2009;28:445–60.PubMedCrossRef Zhang Y, Zhang M, Dong H, Yong S, Li X, Olashaw N, et al. Deacetylation of cortactin by SIRT1 promotes cell migration. Oncogene. 2009;28:445–60.PubMedCrossRef
10.
Zurück zum Zitat Chen HC, Jeng YM, Yuan RH, Hsu HC, Chen YL. SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis. Ann Surg Oncol. 2012;19:2011–9.PubMedCrossRef Chen HC, Jeng YM, Yuan RH, Hsu HC, Chen YL. SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis. Ann Surg Oncol. 2012;19:2011–9.PubMedCrossRef
11.
Zurück zum Zitat Sung JY, Kim R, Kim JE, Lee J. Balance between SIRT1 and DBC1 expression is lost in breast cancer. Cancer Sci. 2010;101:1738–44.PubMedCrossRef Sung JY, Kim R, Kim JE, Lee J. Balance between SIRT1 and DBC1 expression is lost in breast cancer. Cancer Sci. 2010;101:1738–44.PubMedCrossRef
12.
Zurück zum Zitat Feng AN, Zhang LH, Fan XS, Huang Q, Ye Q, Wu HY, et al. Expression of SIRT1 in gastric cardiac cancer and its clinicopathologic significance. Int J Surg Pathol. 2011;19:743–50.PubMedCrossRef Feng AN, Zhang LH, Fan XS, Huang Q, Ye Q, Wu HY, et al. Expression of SIRT1 in gastric cardiac cancer and its clinicopathologic significance. Int J Surg Pathol. 2011;19:743–50.PubMedCrossRef
13.
Zurück zum Zitat Zhao G, Cui J, Zhang JG, Qin Q, Chen Q, Yin T, et al. SIRT1 RNAi knockdown induces apoptosis and senescence, inhibits invasion and enhances chemosensitivity in pancreatic cancer cells. Gene Ther. 2011;18:920–8.PubMedCrossRef Zhao G, Cui J, Zhang JG, Qin Q, Chen Q, Yin T, et al. SIRT1 RNAi knockdown induces apoptosis and senescence, inhibits invasion and enhances chemosensitivity in pancreatic cancer cells. Gene Ther. 2011;18:920–8.PubMedCrossRef
14.
Zurück zum Zitat Stunkel W, Peh BK, Tan YC, Nayagam VM, Wang X, Salto-Tellez M, et al. Function of the SIRT1 protein deacetylase in cancer. Biotechnol J. 2007;2:1360–8.PubMedCrossRef Stunkel W, Peh BK, Tan YC, Nayagam VM, Wang X, Salto-Tellez M, et al. Function of the SIRT1 protein deacetylase in cancer. Biotechnol J. 2007;2:1360–8.PubMedCrossRef
15.
Zurück zum Zitat Kabra N, Li Z, Chen L, Li B, Zhang X, Wang C, et al. SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. J Biol Chem. 2009;284:18210–7.PubMedCentralPubMedCrossRef Kabra N, Li Z, Chen L, Li B, Zhang X, Wang C, et al. SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. J Biol Chem. 2009;284:18210–7.PubMedCentralPubMedCrossRef
16.
Zurück zum Zitat Jang SH, Min KW, Paik SS, Jang KS. Loss of SIRT1 histone deacetylase expression associates with tumour progression in colorectal adenocarcinoma. J Clin Pathol. 2012;65:735–9.PubMedCrossRef Jang SH, Min KW, Paik SS, Jang KS. Loss of SIRT1 histone deacetylase expression associates with tumour progression in colorectal adenocarcinoma. J Clin Pathol. 2012;65:735–9.PubMedCrossRef
18.
Zurück zum Zitat Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y. Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem. 2007;282:6823–32.PubMedCrossRef Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y. Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem. 2007;282:6823–32.PubMedCrossRef
19.
Zurück zum Zitat Byles V, Chmilewski LK, Wang J, Zhu L, Forman LW, Faller DV, et al. Aberrant cytoplasm localization and protein stability of SIRT1 is regulated by PI3K/IGF-1R signaling in human cancer cells. Int J Biol Sci. 2010;6:599–612.PubMedCentralPubMedCrossRef Byles V, Chmilewski LK, Wang J, Zhu L, Forman LW, Faller DV, et al. Aberrant cytoplasm localization and protein stability of SIRT1 is regulated by PI3K/IGF-1R signaling in human cancer cells. Int J Biol Sci. 2010;6:599–612.PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Eades G, Yao Y, Yang M, Zhang Y, Chumsri S, Zhou Q. miR-200a regulates SIRT1 expression and epithelial to mesenchymal transition (EMT)-like transformation in mammary epithelial cells. J Biol Chem. 2011;286:25992–6002.PubMedCentralPubMedCrossRef Eades G, Yao Y, Yang M, Zhang Y, Chumsri S, Zhou Q. miR-200a regulates SIRT1 expression and epithelial to mesenchymal transition (EMT)-like transformation in mammary epithelial cells. J Biol Chem. 2011;286:25992–6002.PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Chu F, Chou PM, Zheng X, Mirkin BL, Rebbaa A. Control of multidrug resistance gene mdr1 and cancer resistance to chemotherapy by the longevity gene sirt1. Cancer Res. 2005;65:10183–7.PubMedCrossRef Chu F, Chou PM, Zheng X, Mirkin BL, Rebbaa A. Control of multidrug resistance gene mdr1 and cancer resistance to chemotherapy by the longevity gene sirt1. Cancer Res. 2005;65:10183–7.PubMedCrossRef
Metadaten
Titel
Clinicopathological significance of SIRT1 expression in colorectal adenocarcinoma
verfasst von
Liang Lv
Zhanlong Shen
Jizhun Zhang
Hui Zhang
Jianqiang Dong
Yichao Yan
Fangfang Liu
Kewei Jiang
Yingjiang Ye
Shan Wang
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 6/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0965-9

Weitere Artikel der Ausgabe 6/2014

Medical Oncology 6/2014 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.