Skip to main content
Top
Published in: Journal of Gastroenterology 1/2010

01-01-2010 | Original Article—Alimentary Tract

Increased expression of miR-421 in human gastric carcinoma and its clinical association

Authors: Zhen Jiang, Junming Guo, Bingxiu Xiao, Ying Miao, Rong Huang, Dong Li, Yuanyuan Zhang

Published in: Journal of Gastroenterology | Issue 1/2010

Login to get access

Abstract

Background

Gastric cancer is a worldwide cancer with poor prognosis. Identification of diagnostic biomarkers and effective therapeutic targets is important in the treatment and diagnosis of gastric cancer. Recently, researchers have found that microRNAs play several important roles in carcinogenesis. The purpose of this study was to investigate the relationships between miR-421 expression patterns in human gastric cancer tissues with clinicopathological features.

Methods

Sixty gastric carcinoma and 18 non-tumor tissues were collected from the Secondary Hospital of Ningbo, China. For quantitative detection of the expression level of miR-421, total RNA was extracted and then reverse transcription-polymerase chain reaction was performed. The relationship between miR-421 expression in gastric cancer and clinicopathological features was analyzed. After miR-421 inhibitor was transfected into gastric cancer cells, cell growth was measured by MTT assay. Finally, the expression of its target genes was detected by Western blotting.

Results

The miR-421 was over-expressed in 73.33% (44/60) of the gastric cancer samples examined. Over-expression of miR-421 in gastric cancer tissues was not found associated with clinicopathological features. The positive detection rate of miR-421 was higher than that of serum carcino-embryonic antigen (χ2 = 39.811, P < 0.001). Inhibition of miR-421 expression decreased the growth of both MGC-803 and SGC-7901 gastric cancer cells in vitro, with up-regulating the expression of its cancer-related target genes, CBX7 and RBMXL1.

Conclusions

miR-421 may involve in the early stage of stomach carcinogenesis and could be used as an efficient diagnostic biomarker.
Literature
1.
2.
go back to reference Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulated the proapoptotic gene hid in Drosophila. Cell. 2003;113:25–36.CrossRefPubMed Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulated the proapoptotic gene hid in Drosophila. Cell. 2003;113:25–36.CrossRefPubMed
3.
go back to reference Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65:6029–33.CrossRefPubMed Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65:6029–33.CrossRefPubMed
4.
go back to reference Xu P, Vernooy SY, Guo M, Hay BA. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol. 2003;13:790–5.CrossRefPubMed Xu P, Vernooy SY, Guo M, Hay BA. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol. 2003;13:790–5.CrossRefPubMed
5.
go back to reference Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.CrossRefPubMed Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.CrossRefPubMed
6.
go back to reference Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75:855–62.CrossRefPubMed Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75:855–62.CrossRefPubMed
7.
go back to reference Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–6.CrossRefPubMed Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–6.CrossRefPubMed
8.
9.
go back to reference Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.CrossRefPubMed Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.CrossRefPubMed
10.
go back to reference Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002;99:15524–9.CrossRefPubMed Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002;99:15524–9.CrossRefPubMed
11.
go back to reference Guo JM, Miao Y, Xiao BX, Huan R, Jiang Z, Meng D, et al. Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol. 2009;24:652–7.CrossRefPubMed Guo JM, Miao Y, Xiao BX, Huan R, Jiang Z, Meng D, et al. Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol. 2009;24:652–7.CrossRefPubMed
12.
go back to reference Sobin LH, Wittekind CH. TNM classification of malignant tumors. 5th ed. New York: Wiley; 1997. p. 59–62. Sobin LH, Wittekind CH. TNM classification of malignant tumors. 5th ed. New York: Wiley; 1997. p. 59–62.
13.
go back to reference Solcia E, Capella C. Endocrine tumours of the gastrointestinal tract. In: Solcia E, Klöppel G, Sobin LH, editors. Histological typing of endocrine tumours. 2nd ed. Berlin: Springer; 2000. p. 61–8. Solcia E, Capella C. Endocrine tumours of the gastrointestinal tract. In: Solcia E, Klöppel G, Sobin LH, editors. Histological typing of endocrine tumours. 2nd ed. Berlin: Springer; 2000. p. 61–8.
14.
go back to reference Xiao B, Guo J, Miao Y, Jiang Z, Huan R, Zhang Y, et al. Detection of miR-106a in gastric carcinoma and its clinical significance. Clin Chim Acta. 2009;400:97–102.CrossRefPubMed Xiao B, Guo J, Miao Y, Jiang Z, Huan R, Zhang Y, et al. Detection of miR-106a in gastric carcinoma and its clinical significance. Clin Chim Acta. 2009;400:97–102.CrossRefPubMed
15.
go back to reference Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.CrossRefPubMed Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.CrossRefPubMed
16.
go back to reference Peng JJ, Cai SJ, Lu HF, Cai GX, Lian P, Guan ZQ, et al. Predicting prognosis of rectal cancer patients with total mesorectal excision using molecular markers. World J Gastroenterol. 2007;13:3009–15.PubMed Peng JJ, Cai SJ, Lu HF, Cai GX, Lian P, Guan ZQ, et al. Predicting prognosis of rectal cancer patients with total mesorectal excision using molecular markers. World J Gastroenterol. 2007;13:3009–15.PubMed
17.
go back to reference Cummins JM, He Y, Leary RJ, Pushkaran B, Liggins AP, Pulford Kl, et al. The colorectal microRNAome. Proc Natl Acad Sci USA. 2006;103:3687–92.CrossRefPubMed Cummins JM, He Y, Leary RJ, Pushkaran B, Liggins AP, Pulford Kl, et al. The colorectal microRNAome. Proc Natl Acad Sci USA. 2006;103:3687–92.CrossRefPubMed
18.
go back to reference Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129:1401–14.CrossRefPubMed Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129:1401–14.CrossRefPubMed
19.
go back to reference Cui XY, Guo YJ, Yao HR. Analysis of microRNA in drug-resistant breast cancer cell line MCF-7/ADR. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28:1813–5.PubMed Cui XY, Guo YJ, Yao HR. Analysis of microRNA in drug-resistant breast cancer cell line MCF-7/ADR. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28:1813–5.PubMed
20.
go back to reference Takahashi Y, Takeuchi T, Sakamoto J, Touge T, Mai M, Ohkura H, et al. The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study. Gastric Cancer. 2003;6:142–5.CrossRefPubMed Takahashi Y, Takeuchi T, Sakamoto J, Touge T, Mai M, Ohkura H, et al. The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study. Gastric Cancer. 2003;6:142–5.CrossRefPubMed
21.
go back to reference Scott CL, Gil J, Hernando E, ewer A, Iovino N, Aravin A, et al. Role of the chromobox protein CBX7 in lymphomagenesis. Proc Natl Acad Sci USA. 2007;104:5389–94.CrossRefPubMed Scott CL, Gil J, Hernando E, ewer A, Iovino N, Aravin A, et al. Role of the chromobox protein CBX7 in lymphomagenesis. Proc Natl Acad Sci USA. 2007;104:5389–94.CrossRefPubMed
22.
go back to reference Bernard D, Martinez-Leal JF, Rizzo S, Martinez D, Hudson D, Visakorpi T, et al. CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus. Oncogene. 2005;24:5543–51.CrossRefPubMed Bernard D, Martinez-Leal JF, Rizzo S, Martinez D, Hudson D, Visakorpi T, et al. CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus. Oncogene. 2005;24:5543–51.CrossRefPubMed
23.
go back to reference Chao TF, Zhang Y, Yan XQ, Yin B, Gong Y-H, Yuan J-G, et al. MiR-9 regulates the expression of CBX7 in human glioma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2008;30:268–74.PubMed Chao TF, Zhang Y, Yan XQ, Yin B, Gong Y-H, Yuan J-G, et al. MiR-9 regulates the expression of CBX7 in human glioma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2008;30:268–74.PubMed
24.
go back to reference Hinz S, Kempkensteffen C, Christoph F, Yin B, Gong Y-H, Yuan J-G, et al. Expression parameters of the polycomb group proteins BMI1, SUZ12, RING1 and CBX7 in urothelial carcinoma of the bladder and their prognostic relevance. Tumour Biol. 2008;29:323–9.CrossRefPubMed Hinz S, Kempkensteffen C, Christoph F, Yin B, Gong Y-H, Yuan J-G, et al. Expression parameters of the polycomb group proteins BMI1, SUZ12, RING1 and CBX7 in urothelial carcinoma of the bladder and their prognostic relevance. Tumour Biol. 2008;29:323–9.CrossRefPubMed
25.
go back to reference Allante P, Federico A, Berlingieri MT, Bianco M, Ferraro A, Forzati F, et al. Loss of the CBX7 gene expression correlates with a highly malignant phenotype in thyroid cancer. Cancer Res. 2008;68:6770–8.CrossRef Allante P, Federico A, Berlingieri MT, Bianco M, Ferraro A, Forzati F, et al. Loss of the CBX7 gene expression correlates with a highly malignant phenotype in thyroid cancer. Cancer Res. 2008;68:6770–8.CrossRef
26.
go back to reference Martínez-Arribas F, Agudo D, Pollán M, Gómez-Esquer F, Díaz-Gil G, Lucas R, et al. Positive correlation between the expression of X-chromosome RBM genes (RBMX, RBM3, RBM10) and the proapoptotic Bax gene in human breast cancer. J Cell Biochem. 2006;97:1275–82.CrossRefPubMed Martínez-Arribas F, Agudo D, Pollán M, Gómez-Esquer F, Díaz-Gil G, Lucas R, et al. Positive correlation between the expression of X-chromosome RBM genes (RBMX, RBM3, RBM10) and the proapoptotic Bax gene in human breast cancer. J Cell Biochem. 2006;97:1275–82.CrossRefPubMed
27.
go back to reference Su JL, Yang CY, Shih JY, Wei LH, Hsieh CY, Jeng YN, et al. Knockdown of contactin-1 expression suppresses invasion and metastasis of lung adenocarcinoma. Cancer Res. 2006;66:2553–61.CrossRefPubMed Su JL, Yang CY, Shih JY, Wei LH, Hsieh CY, Jeng YN, et al. Knockdown of contactin-1 expression suppresses invasion and metastasis of lung adenocarcinoma. Cancer Res. 2006;66:2553–61.CrossRefPubMed
28.
go back to reference Eckerich C, Zapf S, Ulbricht U, Muller S, Fillbrandt R, Westphal M, et al. Contactin is expressed in human astrocytic gliomas and mediates repulsive effects. Glia. 2006;53:1–12.CrossRefPubMed Eckerich C, Zapf S, Ulbricht U, Muller S, Fillbrandt R, Westphal M, et al. Contactin is expressed in human astrocytic gliomas and mediates repulsive effects. Glia. 2006;53:1–12.CrossRefPubMed
29.
go back to reference Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–9.CrossRefPubMed Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–9.CrossRefPubMed
30.
go back to reference Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.CrossRefPubMed Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.CrossRefPubMed
Metadata
Title
Increased expression of miR-421 in human gastric carcinoma and its clinical association
Authors
Zhen Jiang
Junming Guo
Bingxiu Xiao
Ying Miao
Rong Huang
Dong Li
Yuanyuan Zhang
Publication date
01-01-2010
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 1/2010
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-009-0135-6

Other articles of this Issue 1/2010

Journal of Gastroenterology 1/2010 Go to the issue

Original Article—Liver, Pancreas, and Biliary Tract

Etiology of liver cirrhosis in Japan: a nationwide survey