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

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Tumor Biology

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.

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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

Author information

Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China

    Ling Gao, Dechun Li & Yunliang Wang

  2. Department of Oncology, Suzhou Kowloon Hospital, School of Medicine, Shanghai Jiaotong University, Suzhou, China

    Yijin Yang & Haiyan Xu

  3. Department of Gastrointestinal Surgery, No. 3 People’s Hospital, Wuxi, China

    Ruqian Liu

  4. Department of General Surgery, The East District of Suzhou Municipal Hospital, No. 16 Baita Road, 215000, Suzhou, China

    Han Hong

  5. The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province, Soochow University, Suzhou, China

    Mingde Qin

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  1. Ling Gao
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  2. Yijin Yang
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  3. Haiyan Xu
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  4. Ruqian Liu
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Corresponding author

Correspondence to Han Hong.

Additional information

Ling Gao, Yijin Yang, Haiyan Xu and Ruqian Liu contributed equally to this work.

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Gao, L., Yang, Y., Xu, H. et al. miR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4. Tumor Biol. 35, 8309–8318 (2014). https://doi.org/10.1007/s13277-014-2092-9

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  • DOI: https://doi.org/10.1007/s13277-014-2092-9

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