Inhibition of Annexin A2 gene transcription is a promising molecular target for hepatoma cell proliferation and metastasis

Dong,Zhizhen; Yao,Min; Zhang,Haijian; Wang,Li; Huang,Hua; Yan,Meijuan; Wu,Wei; Yao,Dengfu

doi:10.3892/ol.2013.1663

Inhibition of Annexin A2 gene transcription is a promising molecular target for hepatoma cell proliferation and metastasis

Authors:
- Zhizhen Dong
- Min Yao
- Haijian Zhang
- Li Wang
- Hua Huang
- Meijuan Yan
- Wei Wu
- Dengfu Yao
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Affiliations: Research Centre of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Medical School of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: November 6, 2013 https://doi.org/10.3892/ol.2013.1663
Pages: 28-34

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Abstract

Hepatocyte Annexin A2 (ANXA2) expression is associated with the progression and metastasis of hepatocellular carcinoma (HCC). Circulating ANXA2 levels in HCC patients are significantly higher compared with that of patients with benign liver disease. ANXA2 levels have been found to correlate with hepatitis B virus infection, extrahepatic metastasis and portal vein thrombus. By contrast, ANXA2 levels do not correlate with tumour size and AFP levels. However, the underlying mechanisms of ANXA2 remain obscure. The results of the current study identified that abnormalities in hepatic ANXA2 expression were localised to the cell membrane and cytoplasm of HCC tissues and mainly in the cytoplasm of para‑cancerous tissues. ANXA2 was overexpressed in MHCC97‑H cells which have high metastatic potential. Following specific ANXA2‑small hairpin RNA (shRNA) transfection in vitro, ANXA‑2 was effectively inhibited and the S phase ratio of cells was 27.76%, compared with 36.14% in mock‑treated cells. In addition, the invading cell ratio was reduced in the shRNA‑treated group (52.16%) compared with the mock‑treated group (86.14%). The growth and volume of xenograft tumours in vivo was significantly suppressed (P<0.05) in the shRNA group compared with that of the mock group, indicating that ANXA2 may be a novel and useful target for elucidating molecular mechanisms involving the proliferation and metastasis of HCC.

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1	El-Serag HB: Hepatocellular carcinoma. N Engl J Med. 365:1118–1127. 2011. View Article : Google Scholar : PubMed/NCBI
2	Frenette C and Gish RG: Hepatocellular carcinoma: molecular and genomic guideline for the clinician. Clin Liver Dis. 15:307–321. vii–x. 2011. View Article : Google Scholar : PubMed/NCBI
3	Yeh FS, Yu MC, Mo CC, et al: Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. Cancer Res. 49:2506–2509. 1989.PubMed/NCBI
4	Yao D, Jiang D, Huang Z, et al: Abnormal expression of hepatoma specific gamma-glutamyl transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma. Cancer. 88:761–769. 2000. View Article : Google Scholar
5	Yao M, Yao DF, Bian YZ, et al: Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 10:289–294. 2011. View Article : Google Scholar : PubMed/NCBI
6	Li S, Yao DF, Wang L, et al: Expression characteristics of hypoxia-inducible factor-1α and its clinical values in diagnosis and prognosis of hepatocellular carcinoma. Hepat Mon. 11:821–828. 2011.
7	Alison MR, Nicholson LJ and Lin WR: Chronic inflammation and hepatocellular carcinoma. Recent Results Cancer Res. 185:135–148. 2011. View Article : Google Scholar : PubMed/NCBI
8	Thomas MB and Zhu AX: Hepatocellular carcinoma: the need for progress. J Clin Oncol. 23:2892–2899. 2005. View Article : Google Scholar : PubMed/NCBI
9	Gonzalez SA and Keeffe EB: Diagnosis of hepatocellular carcinoma: role of markers and liver biopsy. Clin Liver Dis. 15:297–306. 2011. View Article : Google Scholar : PubMed/NCBI
10	DuBray BJ Jr, Chapman WC and Anderson CD: Hepatocellular carcinoma: a review of the surgical approaches to management. Mo Med. 108:195–198. 2011.PubMed/NCBI
11	Portolani N, Baiocchi GL, Coniglio A, et al: Limited liver resection: a good indication for the treatment of hepatocellular carcinoma in elderly patients. Jpn J Clin Oncol. 41:1358–1365. 2011. View Article : Google Scholar : PubMed/NCBI
12	Shimizu I, Yao DF, Horie C, et al: Mutations in a hydrophilic part of the core gene of hepatitis C virus in patients with hepatocellular carcinoma in China. J Gastroenterol. 32:47–55. 1997. View Article : Google Scholar : PubMed/NCBI
13	Block TM, Mehta AS, Fimmel CJ and Jordan R: Molecular viral oncology of hepatocellular carcinoma. Oncogene. 22:5093–5107. 2003. View Article : Google Scholar : PubMed/NCBI
14	van Malenstein H, van Pelt J and Verslype C: Molecular classification of hepatocellular carcinoma anno 2011. Eur J Cancer. 47:1789–1797. 2011.PubMed/NCBI
15	Sharma M, Ownbey RT and Sharma MC: Breast cancer cell surface annexin II induces cell migration and neoangiogenesis via tPA dependent plasmin generation. Exp Mol Pathol. 88:278–286. 2010. View Article : Google Scholar : PubMed/NCBI
16	Zheng L, Foley K, Huang L, et al: Tyrosine 23 phosphorylation-dependent cell-surface localization of annexin A2 is required for invasion and metastases of pancreatic cancer. PLoS One. 6:e193902011. View Article : Google Scholar
17	Mohammad HS, Kurokohchi K, Yoneyama H, et al: Annexin A2 expression and phosphorylation are up-regulated in hepatocellular carcinoma. Int J Oncol. 33:1157–1163. 2008.PubMed/NCBI
18	Zhao P, Zhang W, Tang J, et al: Annexin II promotes invasion and migration of human hepatocellular carcinoma cells in vitro via its interaction with HAb18G/CD147. Cancer Sci. 101:387–395. 2010. View Article : Google Scholar
19	Bao H, Jiang M, Zhu M, et al: Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma. Int J Hematol. 90:177–185. 2009. View Article : Google Scholar : PubMed/NCBI
20	Hayes MJ, Longbottom RE, Evans MA and Moss SE: Annexinopathies. Subcell Biochem. 45:1–28. 2007. View Article : Google Scholar
21	Gerke V and Moss SE: Annexins: from structure to function. Physiol Rev. 82:331–371. 2002.PubMed/NCBI
22	Zhang HJ, Yao DF, Yao M, et al: Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma. World J Gastroenterol. 18:5897–5904. 2012. View Article : Google Scholar : PubMed/NCBI
23	Ohno Y, Izumi M, Kawamura T, et al: Annexin II represents metastatic potential in clear-cell renal cell carcinoma. Br J Cancer. 101:287–294. 2009. View Article : Google Scholar : PubMed/NCBI
24	Ruan J, Liu F, Chen X, et al: Inhibition of glypican-3 expression via RNA interference influences the growth and invasive ability of the MHCC97-H human hepatocellular carcinoma cell line. Int J Mol Med. 28:497–503. 2011.PubMed/NCBI
25	Yoon SY, Kim JM, Oh JH, et al: Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags. Int J Oncol. 29:315–327. 2006.
26	Tazi el M, Essadi I, M’rabti H, et al: Systemic treatment and targeted therapy in patients with advanced hepatocellular carcinoma. N Am J Med Sci. 3:167–175. 2011.PubMed/NCBI
27	Grewal T and Enrich C: Annexins - modulators of EGF receptor signalling and trafficking. Cell Signal. 21:847–858. 2009. View Article : Google Scholar : PubMed/NCBI
28	Yao M, Yao DF, Bian YZ, et al: Values of circulating GPC-3 mRNA and alpha-fetoprotein in detecting patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 12:171–179. 2013. View Article : Google Scholar : PubMed/NCBI