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EZH2-specific microRNA-98 inhibits human ovarian cancer stem cell proliferation via regulating the pRb-E2F pathway

Tumor Biology volume 35, pages 7239–7247 (2014)Cite this article

Abstract

The Polycomb group protein, enhancer of zeste homolog 2 (EZH2), plays an important role in transcriptional regulation through chromatin remodeling and interactions with other transcription factors to control cell proliferation and embryonic development. Previous study has shown that EZH2 is important for cell cycle regulation and is highly expressed in human ovarian cancer. Loss of EZH2 inhibits growth of ovarian cancer as well as other human carcinomas. In this study, an expression plasmid of EZH2-targeted microRNA-98 was constructed and transfected into human ovarian cancer stem cells (OCSCs). Seventy-two hours after transfection, cell growth was inhibited and arrested at the G0/G1 transition. p21CIPI/WAF1 was up-regulated, while the CDK2/cyclin E complex and c-Myc were down-regulated. Most importantly, expression levels of E2F1, retinoblastoma protein (pRb), and histone deacetylase 1 (HDAC1) in the pRb–E2F signaling pathway had changed. Furthermore, microRNA-98 suppressed the growth of OCSCs xenograft tumors. Our findings suggest that EZH2-specific microRNA-98 can effectively inhibit cell proliferation in vitro and regulate the pRb–E2F pathway in human OCSCs.

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Acknowledgments

This work was supported by grant from the National Natural Science Foundation of China (No. 81202811) and the Shanghai Municipal Health Bureau Fund (No. 20124320) to Te Liu.

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Affiliations

  1. Shanghai Tenth People’s Hospital, Medical School, Tongji University, Shanghai, 200072, China

    Te Liu & Lengchen Hou

  2. Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200031, China

    Te Liu

  3. Laboratoire PROTEE, Bâtiment R, Université du Sud Toulon-Var, 83957, La Garde Cedex, France

    Yongyi Huang

Authors
  1. Te Liu
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  2. Lengchen Hou
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  3. Yongyi Huang
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Correspondence to Te Liu.

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Liu, T., Hou, L. & Huang, Y. EZH2-specific microRNA-98 inhibits human ovarian cancer stem cell proliferation via regulating the pRb-E2F pathway. Tumor Biol. 35, 7239–7247 (2014). https://doi.org/10.1007/s13277-014-1950-9

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  • DOI: https://doi.org/10.1007/s13277-014-1950-9

Keywords

  • Ovarian cancer stem cells
  • EZH2
  • MicroRNA-98
  • pRb-E2F pathway
  • Cell proliferation