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Tumor Biology

, Volume 35, Issue 7, pp 7239–7247 | Cite as

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

  • Te Liu
  • Lengchen Hou
  • Yongyi Huang
Research 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.

Keywords

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

Notes

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.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Shanghai Tenth People’s Hospital, Medical SchoolTongji UniversityShanghaiChina
  2. 2.Shanghai Geriatric Institute of Chinese Medicine, Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  3. 3.Laboratoire PROTEE, Bâtiment RUniversité du Sud Toulon-VarLa Garde CedexFrance

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