MicroRNA library-based functional screening identified miR-137 as a suppresser of gastric cancer cell proliferation

  • Xiushan Zheng
  • Jiaqiang Dong
  • Taiqian Gong
  • Zhiyong Zhang
  • Ying Wang
  • Yunming Li
  • Yulong Shang
  • Kai Li
  • Gui Ren
  • Bin Feng
  • Juntang Li
  • Qifei Tian
  • Shanhong Tang
  • Li Sun
  • Mengbin Li
  • Hongwei Zhang
  • Daiming Fan
Original Article - Cancer Research

DOI: 10.1007/s00432-014-1847-4

Cite this article as:
Zheng, X., Dong, J., Gong, T. et al. J Cancer Res Clin Oncol (2015) 141: 785. doi:10.1007/s00432-014-1847-4

Abstract

Purposes

Uncontrolled proliferation is a key characteristic of gastric carcinogenesis and the precise mechanisms underlying the altered proliferation behaviors of GC cells have not been clearly elucidated. miRNAs has been suggested to play a crucial role in the pathogenesis and development of various cancers. In the present study, we employed an impedance-based real-time cell electronic sensing (RT-CES) system to detect the effects of ectopically expressed miRNAs on GC cell proliferation.

Methods

miRNA mimics were transfected into gastric cancer cell line SGC7901 and the effect of individual miRNA on the proliferation rate of the cells was measured by the RT-CES system. The screening results were validated with qRT-PCR and miR-137 was selected for further research. The effects of ectopically expressed miR-137 on GC cell growth and cell cycle progress were measured using MTT assay and flow cytometry. The target gene of miR-137 was predicted using different bioinformatics tools and the direct interaction between miR-137 and the 3’-UTR was confirmed with a luciferase reporter assay. The in vivo effect of miR-137 on GC cell proliferation was examined with a tumor-bearing nude mouse model. The correlation between miR-137 expression and patients’ prognosis was explored in a cohort of 38 patients. Prognosis was explored in a cohort of 38 patients.

Results

Ectopic expression of miR-137 was sufficient to inhibit GC cell proliferation both in vitro and in vivo. Bioinformatics prediction and luciferase reporter assay revealed CDK6 as a target gene through which miR-137 exerted an inhibitory function. Moreover, miR-137 expression positively correlated with better prognosis.

Conclusion

Our data indicated an important regulatory role of miR-137 in GC cell proliferation and that it may be explored as a prognostic marker for GC.

Keywords

miR-137 Gastric cancer Cell proliferation CDK6 Real-time cell electronic sensing (RT-CES) system 

Supplementary material

432_2014_1847_MOESM1_ESM.doc (312 kb)
Supplementary material 1 (DOC 312 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Xiushan Zheng
    • 1
    • 2
  • Jiaqiang Dong
    • 1
  • Taiqian Gong
    • 1
    • 3
  • Zhiyong Zhang
    • 1
  • Ying Wang
    • 1
  • Yunming Li
    • 2
  • Yulong Shang
    • 1
  • Kai Li
    • 1
  • Gui Ren
    • 1
  • Bin Feng
    • 1
  • Juntang Li
    • 4
  • Qifei Tian
    • 1
  • Shanhong Tang
    • 1
  • Li Sun
    • 1
  • Mengbin Li
    • 1
  • Hongwei Zhang
    • 1
  • Daiming Fan
    • 1
  1. 1.State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anChina
  2. 2.Department of Thoracic SurgeryGeneral Hospital of Chengdu Military CommandChengduChina
  3. 3.Department of Thoracic Surgery, Daping HospitalThird Military Medical UniversityChongqingChina
  4. 4.State Key Laboratory of Cancer Biology, Department of ImmunologyFourth Military Medical UniversityXi’anChina