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Digestive Diseases and Sciences

, Volume 59, Issue 8, pp 1754–1763 | Cite as

miR-1303 Targets Claudin-18 Gene to Modulate Proliferation and Invasion of Gastric Cancer Cells

  • Shi-jie Zhang
  • Jian-fang Feng
  • Lei Wang
  • Wei Guo
  • Yu-wen Du
  • Liang Ming
  • Guo-qiang ZhaoEmail author
Original Article

Abstract

Background

MicroRNAs have emerged as important gene regulators and are recognized as important molecules in carcinogenesis. However, the effects of microRNA-1303 (miR-1303) on gastric cancer (GC) cells and the upstream regulation of GC-associated claudin-18 gene (CLDN18) remain unclear. miR-1303 may be involved in the tumorigenesis of GC by targeting CLDN18.

Aims

The purpose of this study was to explore the effect of miR-1303 targeting of CLDN18 on the proliferation, migration and invasion of human GC cells.

Methods

The expression of miR-1303 and claudin-18 in GC tissues and gastric cancer cell lines were detected by qRT-PCR and western blotting, respectively. CCK8 and colony formation assays were performed to study the influence of miR-1303 on the proliferation of the GC cell lines. Transwell and wound-healing assays were carried out to investigate the effect of miR-1303 on the invasion and migration of GC cell lines. Luciferase reporter assays, restore assays and western blotting were used to demonstrate whether CLDN18 is a direct target of miR-1303.

Results

miR-1303 was significantly overexpressed whereas claudin-18 was downregulated in GC tissues and cell lines, which was significantly associated with tumor size, location invasion, histologic type and tumor-node-metastasis stage. Cell proliferation rates were reduced, and cell invasion and migratory ability was significantly restricted in miR-1303 inhibitor-transfected groups. miR-1303 could bind to the putative binding sites in CLDN18 mRNA 3′-UTR and visibly lower the expression of claudin-18. The introduction of claudin-18 without 3′-UTR restored the miR-1303 promoting migration function.

Conclusions

Downregulation of miR-1303 can inhibit proliferation, migration and invasion of GC cells by targeting CLDN18.

Keywords

miR-1303 Claudin-18 Stomach neoplasms Proliferation Invasion 

Notes

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Shi-jie Zhang
    • 1
  • Jian-fang Feng
    • 2
  • Lei Wang
    • 3
  • Wei Guo
    • 4
  • Yu-wen Du
    • 5
  • Liang Ming
    • 1
  • Guo-qiang Zhao
    • 5
    Email author
  1. 1.Department of Clinical LaboratoryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Medical College of Henan University of Science and TechnologyLuoyangChina
  3. 3.Department of EmergencyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  4. 4.Henan Academy of Medical and Pharmaceutical SciencesZhengzhou UniversityZhengzhouChina
  5. 5.College of Basic Medical SciencesZhengzhou UniversityZhengzhouChina

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