Skip to main content

Advertisement

SpringerLink
Log in

Downregulation of miR-195 correlates with lymph node metastasis and poor prognosis in colorectal cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

miR-195, one of the miR-16/15/195/424/497 family members, has been shown to play an important role in tumorigenesis, as a tumor suppressor. Here, we assess miR-195 expression in colorectal cancer, which has not been investigated before, and its clinical significance including survival analysis. The in vivo significance of expression of miR-16/15/195/424/497 in matched normal and tumor tissues of colorectal cancers was evaluated using a quantitative real-time RT-PCR. Two colorectal cancer cell lines and 85 colorectal cancer and paired normal patient samples with detailed clinical follow-up information were selected. The statistical significance of these markers for disease prognosis was evaluated using a two-tailed, paired Wilcoxon test. A Kaplan–Meier survival curve was generated following a logrank test. As a result, miR-424 was significantly over-expressed, while miR-15a, miR-15b, miR-16, and miR-195 were downregulated in tumors compared with normal colorectal samples (all P < 0.01). Reduced expression of miR-195 occurred more often in patients with lymph node metastasis and advanced tumor stage (all P < 0.01). Kaplan–Meier survival analysis indicated that patients with reduced miR-195 had a poor overall survival (P < 0.01). Moreover, the multivariate analysis showed that reduced expression of miR-195 was an independent predictor of overall survival. Our data indicate the potential of miR-195 as a novel diagnostic or prognostic biomarker for CRC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–6.

    Article  PubMed  CAS  Google Scholar 

  2. Ahmed MA, et al. CD24 shows early upregulation and nuclear expression but is not a prognostic marker in colorectal cancer. J Clin Pathol. 2009;62:1117–22.

    Article  PubMed  CAS  Google Scholar 

  3. Morris EJ, Maughan NJ, Forman D, Quirke P. Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology. Gut. 2007;56:1419–25.

    Article  PubMed  Google Scholar 

  4. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.

    Article  PubMed  CAS  Google Scholar 

  5. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  PubMed  CAS  Google Scholar 

  6. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.

    Article  PubMed  CAS  Google Scholar 

  7. Croce CM. Oncogenes and cancer. N Engl J Med. 2008;358:502–11.

    Article  PubMed  CAS  Google Scholar 

  8. Slack FJ, Weidhaas JB. MicroRNA in cancer prognosis. N Engl J Med. 2008;359:2720–2.

    Article  PubMed  CAS  Google Scholar 

  9. Schwind S, et al. Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a cancer and leukemia Group B Study. J Clin Oncol. 2010;28:5257–64.

    Google Scholar 

  10. Calin GA, 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.

    Article  PubMed  CAS  Google Scholar 

  11. Cimmino A, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005;102:13944–9.

    Article  PubMed  CAS  Google Scholar 

  12. Linsley PS, et al. Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol. 2007;27:2240–52.

    Article  PubMed  CAS  Google Scholar 

  13. Chen RW, et al. Truncation in CCND1 mRNA alters miR-16–1 regulation in mantle cell lymphoma. Blood. 2008;112:822–9.

    Article  PubMed  CAS  Google Scholar 

  14. Bonci D, et al. The miR-15a-miR-16–1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14:1271–7.

    Article  PubMed  CAS  Google Scholar 

  15. He L, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.

    Article  PubMed  CAS  Google Scholar 

  16. Kulda V, et al. Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. Cancer Genet Cytogenet. 2010;200:154–60.

    Google Scholar 

  17. Schetter AJ, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.

    Article  PubMed  CAS  Google Scholar 

  18. Slaby O, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72:397–402.

    Article  PubMed  CAS  Google Scholar 

  19. Wang S, et al. Improvement of tissue preparation for laser capture microdissection: application for cell type-specific miRNA expression profiling in colorectal tumors. BMC Genomics. 2010;11:163.

    Google Scholar 

  20. Calin GA, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353:1793–801.

    Article  PubMed  CAS  Google Scholar 

  21. Nicoloso MS, et al. MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer. 2009;9:293–302.

    Article  PubMed  CAS  Google Scholar 

  22. Gaur A, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67:2456–68.

    Article  PubMed  CAS  Google Scholar 

  23. Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17:215–20.

    Google Scholar 

  24. Xu T, et al. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology. 2009;50:113–21.

    Article  PubMed  CAS  Google Scholar 

  25. Flavin RJ, et al. Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma. Mod Pathol. 2009;22:197–205.

    Article  PubMed  CAS  Google Scholar 

  26. Yang H, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008;68:425–33.

    Article  PubMed  CAS  Google Scholar 

  27. Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA. 2008;14:417–24.

    Article  PubMed  CAS  Google Scholar 

  28. Petillo D, et al. MicroRNA profiling of human kidney cancer subtypes. Int J Oncol. 2009;35:109–14.

    Article  PubMed  CAS  Google Scholar 

  29. Wang YX, et al. Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis. J Dig Dis. 2010;11:50–4.

    Google Scholar 

  30. Liu Q, et al. miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res. 2008;36:5391–404.

    Article  PubMed  CAS  Google Scholar 

  31. Xia H, et al. MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. Biochem Biophys Res Commun. 2009;380:205–10.

    Article  PubMed  CAS  Google Scholar 

  32. Xia L, et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 2008;123:372–9.

    Article  PubMed  CAS  Google Scholar 

  33. Staub E, et al. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer. Mol Cancer. 2006;5:37.

    Google Scholar 

  34. Schumacher P, et al. The metastatic lymph node ratio predicts survival in colon cancer. Am J Surg. 2007;194:827–31 discussion 31–2.

    Google Scholar 

  35. Mitchell PS, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Yan Wang and Jinyong Zhou for help with real-time RT-PCR. This work was in part supported by National Basic Research Priorities Program 973 Project (2011CB707702) from the Ministry of Science and Technology of China, and National Natural Science Foundation of China (30970813, 30930028).

Conflict of interest

The authors have no conflict of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Pathology, Nanjing University School of Medicine/Nanjing Jinling Hospital, Nanjing, 210002, People’s Republic of China

    Xueqing Wang, Jiandong Wang, Henghui Ma & Xiaojun Zhou

  2. Department of Radiology, The Center for Molecular Imaging Research, Nanjing Jinling Hospital, Nanjing, 210002, People’s Republic of China

    Jiandong Wang

  3. Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Dong’an Road 130#, Shanghai, 200000, China

    Jin Zhang

Authors
  1. Xueqing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiandong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henghui Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaojun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaojun Zhou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, X., Wang, J., Ma, H. et al. Downregulation of miR-195 correlates with lymph node metastasis and poor prognosis in colorectal cancer. Med Oncol 29, 919–927 (2012). https://doi.org/10.1007/s12032-011-9880-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-9880-5

Keywords

Search

Navigation