Skip to main content
Top
Published in: Medical Oncology 3/2013

01-09-2013 | Original Paper

Up-regulation of Ago2 expression in gastric carcinoma

Authors: Jin Zhang, Xiang-shan Fan, Cai-xia Wang, Biao Liu, Qin Li, Xiao-jun Zhou

Published in: Medical Oncology | Issue 3/2013

Login to get access

Abstract

Argonaute (Ago) proteins have been demonstrated to be widely expressed and involved in post-transcriptional gene silencing and thus play key roles in carcinogenesis. Nevertheless, little is known about the specific role of Ago2 in gastric cancer (GC). Thus, we aimed to study the expression of Ago2 in 363 primary GC, 8 corresponding lymph node metastases and 10 non-neoplastic surrounding gastric epithelium tissues by immunohistochemical analyses and tissue microarray. The expression of Ago2 was also correlated with clinicopathological characteristics and HER-2 status. Ago2 expression levels in primary GC and corresponding lymph node metastases were significantly higher compared with healthy controls (P < 0.05). But, there was no difference of Ago2 between GC and its metastatic lymph node (P > 0.05). Ago2 up-regulation had no correlation with GC patients’ age, tumor location, tumor size, gross morphology or tumor infiltration. However, we found that Ago2 was different between HER-2 positive and HER-2 negative groups (P = 0.044), which had been demonstrated to be related to GC prognosis. And there was a great correlation between Ago2 expression and the tumor differentiation (P = 0.007), lymph node invasion (P = 0.000) and clinical stage (P = 0.006). Interestingly, Ago2 was also correlated to patients’ gender (P = 0.004), which may suggest a possible role of hormonal signal in the mechanisms of Ago2. Thus, our results suggested that up-regulation of Ago2 may play an important role in GC carcinogenesis and progression. Further studies on the cellular functions of Ago2 need to address these issues.
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.PubMedCrossRef Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.PubMedCrossRef
2.
go back to reference Jing JJ, Liu HY, Hao JK, Wang LN, Wang YP, et al. Gastric cancer incidence and mortality in Zhuanghe, China, between 2005 and 2010. World J Gastroenterol. 2012;18(11):1262–9.PubMedCrossRef Jing JJ, Liu HY, Hao JK, Wang LN, Wang YP, et al. Gastric cancer incidence and mortality in Zhuanghe, China, between 2005 and 2010. World J Gastroenterol. 2012;18(11):1262–9.PubMedCrossRef
3.
go back to reference Lima RT, Busacca S, Almeida GM, Gaudino G, Fennell DA, et al. MicroRNA regulation of core apoptosis pathways in cancer. Eur J Cancer. 2011;47(2):163–74.PubMedCrossRef Lima RT, Busacca S, Almeida GM, Gaudino G, Fennell DA, et al. MicroRNA regulation of core apoptosis pathways in cancer. Eur J Cancer. 2011;47(2):163–74.PubMedCrossRef
4.
go back to reference Van Wynsberghe PM, Chan SP, Slack FJ, Pasquinelli AE. Analysis of microRNA expression and function. Methods Cell Biol. 2011;106:219–52.PubMedCrossRef Van Wynsberghe PM, Chan SP, Slack FJ, Pasquinelli AE. Analysis of microRNA expression and function. Methods Cell Biol. 2011;106:219–52.PubMedCrossRef
5.
go back to reference Sinkovics JG. Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review). Int J Oncol. 2012;40(2):305–49.PubMed Sinkovics JG. Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review). Int J Oncol. 2012;40(2):305–49.PubMed
6.
go back to reference Sandhu S, Garzon R. Potential applications of microRNAs in cancer diagnosis, prognosis, and treatment. Semin Oncol. 2011;38(6):781–7.PubMedCrossRef Sandhu S, Garzon R. Potential applications of microRNAs in cancer diagnosis, prognosis, and treatment. Semin Oncol. 2011;38(6):781–7.PubMedCrossRef
7.
go back to reference Hui A, How C, Ito E, Liu FF. Micro-RNAs as diagnostic or prognostic markers in human epithelial malignancies. BMC Cancer. 2011;30(11):500.CrossRef Hui A, How C, Ito E, Liu FF. Micro-RNAs as diagnostic or prognostic markers in human epithelial malignancies. BMC Cancer. 2011;30(11):500.CrossRef
8.
go back to reference Murray MY, Rushworth SA, MacEwan DJ. MicroRNAs as a new therapeutic target towards leukaemia signalling. Cell Signal. 2012;24(2):363–8.PubMedCrossRef Murray MY, Rushworth SA, MacEwan DJ. MicroRNAs as a new therapeutic target towards leukaemia signalling. Cell Signal. 2012;24(2):363–8.PubMedCrossRef
9.
go back to reference Song MY, Pan KF, Su HJ, Zhang L, Ma JL, et al. Identification of Serum MicroRNAs as novel non-invasive biomarkers for early detection of gastric cancer. PLoS ONE. 2012;7(3):e33608.PubMedCrossRef Song MY, Pan KF, Su HJ, Zhang L, Ma JL, et al. Identification of Serum MicroRNAs as novel non-invasive biomarkers for early detection of gastric cancer. PLoS ONE. 2012;7(3):e33608.PubMedCrossRef
10.
go back to reference Wang D, Zhang Z, O’Loughlin E, Lee T, Houel S, et al. Quantitative functions of Argonaute proteins in mammalian development. Genes Dev. 2012;26(7):693–704.PubMedCrossRef Wang D, Zhang Z, O’Loughlin E, Lee T, Houel S, et al. Quantitative functions of Argonaute proteins in mammalian development. Genes Dev. 2012;26(7):693–704.PubMedCrossRef
11.
go back to reference O’Carroll D, Mecklenbrauker I, Das PP, Santana A, Koenig U, et al. A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev. 2007;21(16):1999–2004.PubMedCrossRef O’Carroll D, Mecklenbrauker I, Das PP, Santana A, Koenig U, et al. A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev. 2007;21(16):1999–2004.PubMedCrossRef
12.
go back to reference Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, et al. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell. 2004;15(2):185–97.PubMedCrossRef Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, et al. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell. 2004;15(2):185–97.PubMedCrossRef
13.
go back to reference Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual (7th ed). New York: Springer; 2010. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual (7th ed). New York: Springer; 2010.
14.
go back to reference Rüschoff J, Dietel M, Baretton G, Arbogast S, Walch A, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457(3):299–307.PubMedCrossRef Rüschoff J, Dietel M, Baretton G, Arbogast S, Walch A, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457(3):299–307.PubMedCrossRef
15.
go back to reference Kavanagh DO, Chambers G, O’Grady L, Barry KM, Waldron RP, et al. Is overexpression of HER-2 a predictor of prognosis in colorectal cancer? BMC Cancer. 2009;1(9):1.CrossRef Kavanagh DO, Chambers G, O’Grady L, Barry KM, Waldron RP, et al. Is overexpression of HER-2 a predictor of prognosis in colorectal cancer? BMC Cancer. 2009;1(9):1.CrossRef
16.
go back to reference Zhang J, Zhan N, Dong WG. Altered expression of selenium-binding protein 1 in gastric carcinoma and precursor lesions. Med Oncol. 2011;28(4):951–7.PubMedCrossRef Zhang J, Zhan N, Dong WG. Altered expression of selenium-binding protein 1 in gastric carcinoma and precursor lesions. Med Oncol. 2011;28(4):951–7.PubMedCrossRef
17.
go back to reference Papaconstantinou I, Karakatsanis A, Gazouli M, Polymeneas G, Voros D. The role of microRNAs in liver cancer. Eur J Gastroenterol Hepatol. 2012;24(3):223–8.PubMedCrossRef Papaconstantinou I, Karakatsanis A, Gazouli M, Polymeneas G, Voros D. The role of microRNAs in liver cancer. Eur J Gastroenterol Hepatol. 2012;24(3):223–8.PubMedCrossRef
18.
go back to reference Majumder S, Jacob ST. Emerging role of microRNAs in drug-resistant breast cancer. Gene Expr. 2011;15(3):141–51.PubMedCrossRef Majumder S, Jacob ST. Emerging role of microRNAs in drug-resistant breast cancer. Gene Expr. 2011;15(3):141–51.PubMedCrossRef
19.
go back to reference Fassan M, Croce CM, Rugge M. miRNAs in precancerous lesions of the gastrointestinal tract. World J Gastroenterol. 2011;17(48):5231–9.PubMedCrossRef Fassan M, Croce CM, Rugge M. miRNAs in precancerous lesions of the gastrointestinal tract. World J Gastroenterol. 2011;17(48):5231–9.PubMedCrossRef
20.
go back to reference Schoenberg DR. Mechanisms of endonuclease-mediated mRNA decay. Wiley Interdiscip Rev RNA. 2011;2(4):582–600.PubMedCrossRef Schoenberg DR. Mechanisms of endonuclease-mediated mRNA decay. Wiley Interdiscip Rev RNA. 2011;2(4):582–600.PubMedCrossRef
21.
go back to reference Cullen BR. Viruses and microRNAs: RISCy interactions with serious consequences. Genes Dev. 2011;25(18):1881–94.PubMedCrossRef Cullen BR. Viruses and microRNAs: RISCy interactions with serious consequences. Genes Dev. 2011;25(18):1881–94.PubMedCrossRef
22.
go back to reference Diederichs S, Haber DA. Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression. Cell. 2007;131(6):1097–108.PubMedCrossRef Diederichs S, Haber DA. Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression. Cell. 2007;131(6):1097–108.PubMedCrossRef
23.
go back to reference Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell. 2005;123(4):607–20.PubMedCrossRef Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell. 2005;123(4):607–20.PubMedCrossRef
24.
go back to reference Leuschner PJ, Ameres SL, Kueng S, Martinez J. Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep. 2006;7(3):314–20.PubMedCrossRef Leuschner PJ, Ameres SL, Kueng S, Martinez J. Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep. 2006;7(3):314–20.PubMedCrossRef
25.
go back to reference Rand TA, Petersen S, Du F, Wang X. Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell. 2005;123(4):621–9.PubMedCrossRef Rand TA, Petersen S, Du F, Wang X. Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell. 2005;123(4):621–9.PubMedCrossRef
26.
go back to reference Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, et al. A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science. 2010;328(5986):1694–8.PubMedCrossRef Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, et al. A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science. 2010;328(5986):1694–8.PubMedCrossRef
27.
go back to reference Yoo NJ, Hur SY, Kim MS, Lee JY, Lee SH. Immunohistochemical analysis of RNA-induced silencing complex-related proteins AGO2 and TNRC6A in prostate and esophageal cancers. APMIS. 2010;118(4):271–6.PubMedCrossRef Yoo NJ, Hur SY, Kim MS, Lee JY, Lee SH. Immunohistochemical analysis of RNA-induced silencing complex-related proteins AGO2 and TNRC6A in prostate and esophageal cancers. APMIS. 2010;118(4):271–6.PubMedCrossRef
28.
go back to reference Li L, Yu C, Gao H, Li Y. Argonaute proteins: Potential biomarkers for human colon cancer. BMC Cancer. 2010;10:38.PubMedCrossRef Li L, Yu C, Gao H, Li Y. Argonaute proteins: Potential biomarkers for human colon cancer. BMC Cancer. 2010;10:38.PubMedCrossRef
29.
go back to reference Chang SS, Smith I, Glazer C, Hennessey P, Califano JA. EIF2C is overexpressed and amplified in head and neck squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2010;72:337–43.PubMedCrossRef Chang SS, Smith I, Glazer C, Hennessey P, Califano JA. EIF2C is overexpressed and amplified in head and neck squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2010;72:337–43.PubMedCrossRef
30.
go back to reference Sand M, Skrygan M, Georgas D, Arenz C, Gambichler T, et al. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components Argonaute-1, Argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer. Mol Carcinog; 2011. Sand M, Skrygan M, Georgas D, Arenz C, Gambichler T, et al. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components Argonaute-1, Argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer. Mol Carcinog; 2011.
31.
go back to reference Papachristou DJ, Sklirou E, Corradi D, Grassani C, Kontogeorgakos V, et al. Immunohistochemical analysis of the endoribonucleases Drosha, Dicer and Ago2 in smooth muscle tumours of soft tissues. Histopathology; 2012. Papachristou DJ, Sklirou E, Corradi D, Grassani C, Kontogeorgakos V, et al. Immunohistochemical analysis of the endoribonucleases Drosha, Dicer and Ago2 in smooth muscle tumours of soft tissues. Histopathology; 2012.
32.
go back to reference Zhang X, Graves P, Zeng Y. Overexpression of human Argonaute2 inhibits cell and tumor growth. Biochim Biophys Acta. 2012;1830(3):2553–61.CrossRef Zhang X, Graves P, Zeng Y. Overexpression of human Argonaute2 inhibits cell and tumor growth. Biochim Biophys Acta. 2012;1830(3):2553–61.CrossRef
33.
go back to reference Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med. 2005;353:1652–4.PubMedCrossRef Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med. 2005;353:1652–4.PubMedCrossRef
34.
go back to reference Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004;4:361–70.PubMedCrossRef Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004;4:361–70.PubMedCrossRef
35.
go back to reference Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9:463–75.PubMedCrossRef Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9:463–75.PubMedCrossRef
36.
go back to reference Naoghare PK, Tak YK, Kim MJ, Han E, Song JM. Knock-down of argonaute 2 (AGO2) induces apoptosis in myeloid leukaemia cells and inhibits siRNA-mediated silencing of transfected oncogenes in HEK-293 cells. Basic Clin Pharmacol Toxicol. 2011;109(4):274–82.PubMedCrossRef Naoghare PK, Tak YK, Kim MJ, Han E, Song JM. Knock-down of argonaute 2 (AGO2) induces apoptosis in myeloid leukaemia cells and inhibits siRNA-mediated silencing of transfected oncogenes in HEK-293 cells. Basic Clin Pharmacol Toxicol. 2011;109(4):274–82.PubMedCrossRef
37.
go back to reference Cheng N, Li Y, Han ZG. Ago2 promotes tumor metastasis via upregulating FAK expression in hepatocellular carcinoma. Hepatology. 2013;57:1906–18.PubMedCrossRef Cheng N, Li Y, Han ZG. Ago2 promotes tumor metastasis via upregulating FAK expression in hepatocellular carcinoma. Hepatology. 2013;57:1906–18.PubMedCrossRef
Metadata
Title
Up-regulation of Ago2 expression in gastric carcinoma
Authors
Jin Zhang
Xiang-shan Fan
Cai-xia Wang
Biao Liu
Qin Li
Xiao-jun Zhou
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/s12032-013-0628-2

Other articles of this Issue 3/2013

Medical Oncology 3/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.