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Tumor Biology

, Volume 36, Issue 5, pp 3221–3229 | Cite as

Let-7b inhibits cell proliferation, migration, and invasion through targeting Cthrc1 in gastric cancer

  • Junbo Yu
  • Jin Feng
  • Xiaofei Zhi
  • Jie Tang
  • Zenliang Li
  • Yong Xu
  • Li Yang
  • Zhibin Hu
  • Zekuan Xu
Research Article

Abstract

Dysregulation of specific microRNAs (miRNAs) is found to play a vital role in carcinogenesis and progression of gastric cancer (GC). In the present study, we investigated the expression profiles of miRNAs in gastric cancer. Let-7b was found downregulated remarkably in gastric cancer tissues and was correlated with Helicobacter pylori infection, tumor stage, and lymphatic metastasis. Ectopic expression of let-7b suppressed the growth, migration, invasion, and tumorigenicity of GC cells, whereas let-7b knockdown promoted these phenotypes. Bioinformatic analysis predicted collagen triple helix repeat containing 1 (Cthrc1) as a direct target of let-7b. Luciferase assay showed that let-7b repressed the activity of Cthrc1 through binding its 3’UTR. Western blotting also confirmed that the protein levels of Cthrc1 were decreased by let-7b. Cthrc1 was significantly upregulated and reversely correlated with let-7b levels in GC. Co-expression of let-7b and Cthrc1 without its 3’UTR could rescue cell growth, migration, and invasion inhibited by let-7b. These results suggest that let-7b may directly target Cthrc1 and function as a tumor suppressor gene in GC.

Keywords

microRNA Let-7b Gastric cancer Cthrc1 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No.812111519 and No.81272712) and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (JX10231801).

Conflicts of interests

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Junbo Yu
    • 1
  • Jin Feng
    • 2
  • Xiaofei Zhi
    • 3
  • Jie Tang
    • 3
  • Zenliang Li
    • 4
  • Yong Xu
    • 2
  • Li Yang
    • 3
  • Zhibin Hu
    • 5
  • Zekuan Xu
    • 3
  1. 1.Department of General Surgerythe Affiliated Hospital of Nantong UniversityNantongChina
  2. 2.Department of General Surgerythe Third Affiliated Hospital of Soochow UniversityChangzhouChina
  3. 3.Department of General Surgerythe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  4. 4.Department of General Surgery, Huai’an First People’s HospitalNanjing Medical UniversityHuai’anChina
  5. 5.Department of Epidemiology and Biostatistics, School of Public HealthNanjing Medical UniversityNanjingChina

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