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Tumor Biology

, Volume 35, Issue 8, pp 8309–8318 | Cite as

miR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4

  • Ling Gao
  • Yijin Yang
  • Haiyan Xu
  • Ruqian Liu
  • Dechun Li
  • Han Hong
  • Mingde Qin
  • Yunliang Wang
Research Article

Abstract

Octamer-binding transcription factor 4 (OCT4) was closely related to pancreatic cancer progression, but its regulation in pancreatic cancer by microRNA (miRNA) is not fully clear. OCT4-positive and OCT4-negative pancreatic cells were isolated by flow cytometry, and it was found that OCT4-positive cells are enriched in transplanted pancreatic cancer cells compared with the primary ones and showed increasing proliferation and sphere formation. The data of miRNA array assay showed that miR-335 in OCT4-positive pancreatic cancer cells was lower than that in the negative ones. The results were confirmed in pancreatic cancer tissue and cell lines. Through expression analysis, it was found that miR-335 was underexpressed in OCT4(+) pancreatic cancer cells purified from primary tumors. Enforced expression of miR-335 in OCT4(+) pancreatic cancer cells inhibited clonogenic expansion and tumor development. miR-335 re-expression in OCT4(+) pancreatic cancer cells was blocked. Systemically delivered miR-335 inhibited pancreatic cancer metastasis and extended animal survival. Of significance, OCT4 was identified and validated as a direct and functional target of miR-335. Taken together, our results provide evidence that miR-335 might inhibit progression and stem cell properties of pancreatic cancer targeting OCT4.

Keywords

miR-335 OCT4 Pancreatic cancer Stem cell Tumorigenesis 

Notes

Acknowledgments

The project was founded by the Post-Graduate Scientific Research Innovation Project of Education Department of Jiangsu Province (CXZZ12_0842), the Open fund of the Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (KJS1230), and Science and Technology Research Project of Science and Technology Bureau of Suzhou City (SYS201330), China.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ling Gao
    • 1
  • Yijin Yang
    • 2
  • Haiyan Xu
    • 2
  • Ruqian Liu
    • 3
  • Dechun Li
    • 1
  • Han Hong
    • 4
  • Mingde Qin
    • 5
  • Yunliang Wang
    • 1
  1. 1.Department of General SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  2. 2.Department of Oncology, Suzhou Kowloon Hospital, School of MedicineShanghai Jiaotong UniversitySuzhouChina
  3. 3.Department of Gastrointestinal SurgeryNo. 3 People’s HospitalWuxiChina
  4. 4.Department of General SurgeryThe East District of Suzhou Municipal HospitalSuzhouChina
  5. 5.The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province, Soochow UniversitySuzhouChina

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