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Genetic variation in microRNA-binding site and prognosis of patients with colorectal cancer

  • Jong Gwang Kim
  • Yee Soo Chae
  • Soo Jung Lee
  • Byung Woog Kang
  • Jae Yong Park
  • Eun-Jin Lee
  • Hyo-Sung JeonEmail author
  • Jun Seok Park
  • Gyu Seog ChoiEmail author
Original Article – Cancer Research

Abstract

Background

Single nucleotide polymorphisms (SNPs) located in the 3′-UTR of miRNA target genes could affect miRNA-mediated gene regulation, thereby contributing to the susceptibility or prognosis of cancer. Accordingly, the present study analyzed SNPs located at putative miRNA-binding sites of the 3′-UTR of various genes and investigated their impact on the prognosis for patients with colorectal cancer.

Materials and methods

In total, 831 consecutive patients (discovery cohort, n = 309; validation cohort, n = 522) with curatively resected colorectal adenocarcinoma were enrolled. Plus, 157 SNPs were selected from an in silico analysis based on several miRNA and HapMap databases. The SNP genotyping was performed using a Sequenom MassARRAY. A luciferase assay was used to investigate whether miR-571 modulated PAUF gene expression when rs12373 was included in the PAUF 3′UTR region.

Results

In the discovery cohort, 18 SNPs were identified as possible prognostic biomarkers in a survival analysis. In the validation cohort, two SNPs (TPST1 rs3757417T>G and PAUF rs12373A>C) were significantly associated with prognosis in the same direction as the discovery cohort when adjusted for age, preoperative carcinoembryonic antigen level, and pathologic stage (discovery + validation cohort; TPST1 rs3757417T>G, disease-free survival (DFS), p value = 0.0004, overall survival (OS), p value = 0.01 in recessive model; PAUF rs12373A>C, DFS, p value = <0.0001, OS, p value = 0.0008 in dominant model). A significantly lower Renilla activity was observed in the rs12373 CC construct when compared with the rs12373 AA construct (p = 0.002).

Conclusion

The current study provides evidence that the TPST1 rs3757417T>G and PAUF rs12373A>C polymorphisms are possible prognostic biomarkers for patients with colorectal cancer.

Keywords

Colorectal cancer MiRNA target gene Polymorphism Prognosis 

Notes

Acknowledgments

This work was supported in part by National Research Foundation (NRF) of Korea Grant funded by the Korean Government (NRF-2011-0015862) and in part by NRF funded by the Ministry of Education (2013R1A1A4A01008144).

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

432_2014_1780_MOESM1_ESM.xlsx (27 kb)
Supplementary material 1 (XLSX 26 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jong Gwang Kim
    • 1
  • Yee Soo Chae
    • 1
  • Soo Jung Lee
    • 1
  • Byung Woog Kang
    • 1
  • Jae Yong Park
    • 2
    • 3
  • Eun-Jin Lee
    • 2
  • Hyo-Sung Jeon
    • 2
    Email author
  • Jun Seok Park
    • 4
  • Gyu Seog Choi
    • 4
    Email author
  1. 1.Department of Oncology/Hematology, Kyungpook National University Medical CenterKyungpook National University School of MedicineDaeguRepublic of Korea
  2. 2.Department of Biochemistry and Cell BiologyKyungpook National University School of MedicineDaeguRepublic of Korea
  3. 3.Department of Internal MedicineKyungpook National University School of MedicineDaeguRepublic of Korea
  4. 4.Colorectal Cancer Center, Kyungpook National University Medical CenterKyungpook National University School of MedicineDaeguRepublic of Korea

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