Skip to main content
Log in

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

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281–297.

    Article  PubMed  CAS  Google Scholar 

  2. Chen CZ. MicroRNAs as oncogenes and tumor suppressors. N Engl J Med 2005;353:1768–1771.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    Article  PubMed  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. 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  Google Scholar 

  8. Shi R, Chiang VL. Facile means for quantifying microRNA expression by real-time PCR. Biotechniques. 2005;39:519–525.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. 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  Google Scholar 

  11. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006;6:857–866.

    Article  PubMed  CAS  Google Scholar 

  12. Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006;6:259–269.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    Article  PubMed  CAS  Google Scholar 

  26. 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;120:1046–1054

    Article  PubMed  CAS  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  Google Scholar 

  29. Xi HQ, Zhao P, Han WD. Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma. World J Gastroentero. 2010;16:1644–1648.

    Article  Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007;449:682–688.

    Article  PubMed  CAS  Google Scholar 

  32. 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  Google Scholar 

  33. 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. 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.

    Article  PubMed  CAS  Google Scholar 

  35. 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.

    Article  PubMed  CAS  Google Scholar 

  36. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by National Science Foundation of China (nos. 30772137 and 30972879) and Specialized Research Fund for the Doctoral Program of Higher Education (no. 200801590006).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhenning Wang.

Additional information

Yeunpo Chiang and Yongxi Song contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chiang, Y., Song, Y., Wang, Z. et al. Aberrant Expression of miR-203 and Its Clinical Significance in Gastric and Colorectal Cancers. J Gastrointest Surg 15, 63–70 (2011). https://doi.org/10.1007/s11605-010-1367-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-010-1367-8

Keywords

Navigation