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Tumor Biology

, Volume 34, Issue 6, pp 3705–3712 | Cite as

microRNA-148a suppresses human gastric cancer cell metastasis by reversing epithelial-to-mesenchymal transition

  • Sui-Han Wang
  • Xu Li
  • Li-Sheng Zhou
  • Zhong-Wei Cao
  • Chao Shi
  • Chong-Zhi Zhou
  • Yu-Gang Wen
  • Yang Shen
  • Ji-Kun Li
Research Article

Abstract

MicroRNAs (miRNAs) are important regulators of gastric cancer development and progression. miR-148a is one of the most frequently and highly downregulated miRNAs in gastric cancer and is associated with advanced clinical stage and poor prognosis. In this study, we investigated the role of miR-148a in gastric cancer metastasis. Levels of miR-148a were determined by qRT-PCR in 60 gastric cancer samples. Cell migration and invasion assays were performed in a stably expressing miRNA-148a gastric cancer cell line established using a lentivirus expression system. Epithelial–mesenchymal transition (EMT) was evaluated using qRT-PCR and Western Blots to detect epithelial marker E-cadherin and mesenchymal marker, vimentin. Luciferase reporter assays were used to identify downstream targets and biological function of miR-148a. Gastric cancer tissue had significantly lower expression of miR-148a compared to non-tumor tissue. Low miR-148a levels were associated with lymph node metastasis, N stage, and blood vessel invasion. miR-148a overexpression inhibited metastasis of gastric cancer cells. miR-148a overexpression also downregulated vimentin expression and upregulated E-cadherin expression, suggesting that miR-148a inhibited EMT. Finally, the SMAD2 gene was identified as the direct and functional target of miR-148a. MiR-148a suppresses gastric cancer metastasis and EMT, likely via SMAD2. Restoration of miR-148a expression could have important implications in gastric cancer therapy.

Keywords

MicroRNA-148a Gastric cancer Epithelial-to-mesenchymal transition Smad2 Metastasis 

Notes

Acknowledgments

This work was supported by Shanghai Roche Pharmaceuticals Ltd.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Sui-Han Wang
    • 1
  • Xu Li
    • 1
  • Li-Sheng Zhou
    • 1
  • Zhong-Wei Cao
    • 2
  • Chao Shi
    • 3
  • Chong-Zhi Zhou
    • 1
  • Yu-Gang Wen
    • 1
  • Yang Shen
    • 1
  • Ji-Kun Li
    • 1
  1. 1.Department of General Surgery, Shanghai First People’s Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  2. 2.Department of Gastroenterology, Shanghai First People’s Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  3. 3.Department of Gastrointestinal SurgeryYixing People’s HospitalYixingPeople’s Republic of China

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