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Published in: Journal of Gastrointestinal Surgery 1/2011

01-01-2011 | Original Article

Aberrant Expression of miR-203 and Its Clinical Significance in Gastric and Colorectal Cancers

Authors: Yeunpo Chiang, Yongxi Song, Zhenning Wang, Yue Chen, Zhenyu Yue, Huimian Xu, Chengzhong Xing, Zhuangkai Liu

Published in: Journal of Gastrointestinal Surgery | Issue 1/2011

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Abstract

Background

MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin, they have been increasingly shown to have aberrant expression in many tumor types. miR-203 has not been comprehensively investigated in gastric and colorectal cancers.

Methods

Total RNA was extracted from tissues of 212 patients with gastric or colorectal cancer as well as from seven gastric and colorectal cell lines. We determined the expression of miR-203 by real-time PCR and calculated using the \( {{2}^{ - }}^{{\Delta \Delta Ct}} \) method. Then, we assessed miR-203 expression and clinicopathologic characteristics. Finally, we studied the effect of miR-203 on cell proliferation in SGC-7901 cells by MTT.

Results

miR-203 has significantly low expression in colorectal cancer tissues (p < 0.001, paired t test) and cancer cell lines compared to non-tumor counterparts. Moreover, low expression of miR-203 was correlated with tumor size (p = 0.015, non-parametric test) and pT stage (p = 0.005) in colorectal cancer. Although expression of miR-203 was not significant in gastric cancer tissues (p = 0.124), interestingly, miR-203 was correlated with tumor size (p = 0.023), macroscopic type (p = 0.045), and pT stage (p = 0.013). Furthermore, we found miR-203 can inhibit the cell proliferation in SGC-7901 cells.

Conclusion

miR-203 may be related to the proliferation and invasion of gastric and colorectal cancers.
Literature
1.
3.
go back to reference Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–15529.PubMedCrossRef Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–15529.PubMedCrossRef
4.
go back to reference Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature 2005;435:834–838.PubMedCrossRef Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature 2005;435:834–838.PubMedCrossRef
5.
go back to reference Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–2261.PubMedCrossRef Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–2261.PubMedCrossRef
6.
go back to reference Chen Y, Song Y, Wang Z, Yue Z, Xu H, Xing C, Liu Z. Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg 2010;14:1170–1179.PubMedCrossRef Chen Y, Song Y, Wang Z, Yue Z, Xu H, Xing C, Liu Z. Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg 2010;14:1170–1179.PubMedCrossRef
7.
go back to reference Chan SH, Wu CW, Li AF, Chi CW, Lin WC. Mir-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res 2008;28:907–911.PubMed Chan SH, Wu CW, Li AF, Chi CW, Lin WC. Mir-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res 2008;28:907–911.PubMed
8.
go back to reference Shi R, Chiang VL. Facile means for quantifying microRNA expression by real-time PCR. Biotechniques. 2005;39:519–525.PubMedCrossRef Shi R, Chiang VL. Facile means for quantifying microRNA expression by real-time PCR. Biotechniques. 2005;39:519–525.PubMedCrossRef
9.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative pcr and the 2 (delta delta c(T)) method. Methods. 2001;25:402–408.PubMedCrossRef Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative pcr and the 2 (delta delta c(T)) method. Methods. 2001;25:402–408.PubMedCrossRef
10.
go back to reference Wang CJ, Zhou ZG, Wang L, Zhou B, Gu J, Chen HY, Sun XF. Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. Dis Markers. 2009;26:27–34.PubMed Wang CJ, Zhou ZG, Wang L, Zhou B, Gu J, Chen HY, Sun XF. Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. Dis Markers. 2009;26:27–34.PubMed
11.
12.
go back to reference Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006;6:259–269.PubMedCrossRef Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006;6:259–269.PubMedCrossRef
13.
go back to reference Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008;68:2094–2105.PubMedCrossRef Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008;68:2094–2105.PubMedCrossRef
14.
go back to reference Feber A, Xi L, Luketich JD, Pennathur A, Landreneau RJ, Wu M, Swanson SJ, Godfrey TE, Litle VR. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg. 2008;135:255–260.PubMedCrossRef Feber A, Xi L, Luketich JD, Pennathur A, Landreneau RJ, Wu M, Swanson SJ, Godfrey TE, Litle VR. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg. 2008;135:255–260.PubMedCrossRef
15.
go back to reference Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J. Mir-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. Carcinogenesis. 2010;31:766–776. Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J. Mir-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. Carcinogenesis. 2010;31:766–776.
16.
go back to reference Bueno MJ, Pérez de Castro I, Gómez de Cedrón M, Santos J, Calin GA, Cigudosa JC, Croce CM, Fernández-Piqueras J, Malumbres M. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13:496–506.PubMedCrossRef Bueno MJ, Pérez de Castro I, Gómez de Cedrón M, Santos J, Calin GA, Cigudosa JC, Croce CM, Fernández-Piqueras J, Malumbres M. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13:496–506.PubMedCrossRef
17.
go back to reference Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, Ambros VR, Israel MA. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67:2456–2468.PubMedCrossRef Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, Ambros VR, Israel MA. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67:2456–2468.PubMedCrossRef
18.
go back to reference Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–198.PubMedCrossRef Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–198.PubMedCrossRef
19.
go back to reference Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P, Taubert H. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 2010;126:73–80.PubMedCrossRef Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P, Taubert H. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 2010;126:73–80.PubMedCrossRef
20.
go back to reference Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P, Sevignani C, Byrne D, Negrini M, Pagano F, Gomella LG, Croce CM, Baffa R. Micro-RNA profiling in kidney and bladder cancers. Urol Oncol. 2007;25:387–392.PubMedCrossRef Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P, Sevignani C, Byrne D, Negrini M, Pagano F, Gomella LG, Croce CM, Baffa R. Micro-RNA profiling in kidney and bladder cancers. Urol Oncol. 2007;25:387–392.PubMedCrossRef
21.
go back to reference Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–7070.PubMedCrossRef Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–7070.PubMedCrossRef
22.
go back to reference Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67:8699–8707.PubMedCrossRef Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67:8699–8707.PubMedCrossRef
23.
go back to reference Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, Gardiman M, Rugge M, Gomella LG, Croce CM, Rosenberg A. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol. 2009;219:214–221.PubMedCrossRef Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, Gardiman M, Rugge M, Gomella LG, Croce CM, Rosenberg A. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol. 2009;219:214–221.PubMedCrossRef
24.
go back to reference Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, Liu CG, Calin GA, Croce CM, Harris CC. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–436.PubMedCrossRef Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, Liu CG, Calin GA, Croce CM, Harris CC. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–436.PubMedCrossRef
25.
go back to reference Quach H, Barreiro LB, Laval G, Zidane N, Patin E, Kidd KK, Kidd JR, Bouchier C, Veuille M, Antoniewski C, Quintana-Murci L. Signatures of purifying and local positive selection in human miRNAs. Am J Hum Genet. 2009;84:316–327.PubMedCrossRef Quach H, Barreiro LB, Laval G, Zidane N, Patin E, Kidd KK, Kidd JR, Bouchier C, Veuille M, Antoniewski C, Quintana-Murci L. Signatures of purifying and local positive selection in human miRNAs. Am J Hum Genet. 2009;84:316–327.PubMedCrossRef
26.
go back to reference Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007;120:1046–1054PubMedCrossRef Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007;120:1046–1054PubMedCrossRef
27.
go back to reference Adachi Y, Oshiro T, Mori M, Maehara Y, Sugimachi K, Tumor size as a simple prognostic indicator for gastric carcinoma. Ann Surg Oncol. 1997;4:137–140.PubMedCrossRef Adachi Y, Oshiro T, Mori M, Maehara Y, Sugimachi K, Tumor size as a simple prognostic indicator for gastric carcinoma. Ann Surg Oncol. 1997;4:137–140.PubMedCrossRef
28.
go back to reference Kim JP, Kim YW, Yang HK, Noh DY. Significant prognostic factors by multivariate analysis of 3926 gastric cancer patients. World J Surg 1994;18:872–878.PubMedCrossRef Kim JP, Kim YW, Yang HK, Noh DY. Significant prognostic factors by multivariate analysis of 3926 gastric cancer patients. World J Surg 1994;18:872–878.PubMedCrossRef
29.
go back to reference Xi HQ, Zhao P, Han WD. Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma. World J Gastroentero. 2010;16:1644–1648.CrossRef Xi HQ, Zhao P, Han WD. Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma. World J Gastroentero. 2010;16:1644–1648.CrossRef
30.
go back to reference Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005;353:1793–1801.PubMedCrossRef Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005;353:1793–1801.PubMedCrossRef
31.
go back to reference Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007;449:682–688.PubMedCrossRef Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007;449:682–688.PubMedCrossRef
32.
go back to reference Yokota T, Ishiyama S, Saito T, Teshima S, Yamada Y, Iwamoto K, Takahashi M, Murata K, Yamauchi H. Is tumor size a prognostic indicator for gastric carcinoma?. Anticancer Res 2002;22:3673–3637.PubMed Yokota T, Ishiyama S, Saito T, Teshima S, Yamada Y, Iwamoto K, Takahashi M, Murata K, Yamauchi H. Is tumor size a prognostic indicator for gastric carcinoma?. Anticancer Res 2002;22:3673–3637.PubMed
33.
go back to reference Hamilton SR, Aaltonen LA. Pathology and Genetics of Tumours of the Digestive System. In Kleihuesv P, Sobin LH ed. World Health Organization Classification of Tumours. IARC: Lyon, 2000, pp 103–142. Hamilton SR, Aaltonen LA. Pathology and Genetics of Tumours of the Digestive System. In Kleihuesv P, Sobin LH ed. World Health Organization Classification of Tumours. IARC: Lyon, 2000, pp 103–142.
34.
go back to reference Agirre X, Vilas-Zornoza A, Jiménez-Velasco A, Martin-Subero JI, Cordeu L, Gárate L, San José-Eneriz E, Abizanda G, Rodríguez-Otero P, Fortes P, Rifón J, Bandrés E, Calasanz MJ, Martín V, Heiniger A, Torres A, Siebert R, Román-Gomez J, Prósper F. Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia. Cancer Res 2009;69:4443–4453.PubMedCrossRef Agirre X, Vilas-Zornoza A, Jiménez-Velasco A, Martin-Subero JI, Cordeu L, Gárate L, San José-Eneriz E, Abizanda G, Rodríguez-Otero P, Fortes P, Rifón J, Bandrés E, Calasanz MJ, Martín V, Heiniger A, Torres A, Siebert R, Román-Gomez J, Prósper F. Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia. Cancer Res 2009;69:4443–4453.PubMedCrossRef
35.
go back to reference Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005;433:769–773.PubMedCrossRef Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005;433:769–773.PubMedCrossRef
36.
go back to reference Luan S, Sun L, Huang F. MicroRNA-34a: a novel tumor suppressor in p53-mutant glioma cell line U251. Arch Med Res 2010;41:67–74.PubMedCrossRef Luan S, Sun L, Huang F. MicroRNA-34a: a novel tumor suppressor in p53-mutant glioma cell line U251. Arch Med Res 2010;41:67–74.PubMedCrossRef
Metadata
Title
Aberrant Expression of miR-203 and Its Clinical Significance in Gastric and Colorectal Cancers
Authors
Yeunpo Chiang
Yongxi Song
Zhenning Wang
Yue Chen
Zhenyu Yue
Huimian Xu
Chengzhong Xing
Zhuangkai Liu
Publication date
01-01-2011
Publisher
Springer-Verlag
Published in
Journal of Gastrointestinal Surgery / Issue 1/2011
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-010-1367-8

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