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Hes1/Hes5 Gene Inhibits Differentiation via Down-Regulating Hash1 and Promotes Proliferation in Cervical Carcinoma Cells
  1. Jia Liu, PhD*,
  2. Wei-Guo Lu, PhD*,
  3. Feng Ye, PhD,
  4. Xiao-dong Cheng, MD*,
  5. Die Hong, PhD,
  6. Ying Hu, MD,
  7. Huai-zeng Chen, MD and
  8. Xing Xie, MD*
  1. *Department of Gynecologic Oncology, and
  2. Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  1. Address correspondence and reprint requests to Wei-Guo Lu, PhD, Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd No. 2, Hangzhou, 310006, China. E-mail: Lwg{at}hzcnc.com.

Abstract

Introduction: Hairy and enhancer of split 1 (Hes1) and Hes5 are target genes for the mammalian Notch pathway, which are highly expressed in epithelia in the process of embryogenesis or in neural stem cells, inhibit cell differentiation via the Notch-Hes-Hash signaling, and promote the survival of stem cells. Either Hes1 or Hes5 overactivation is likely to affect cell differentiation, thereby resulting in carcinogenesis.

Methods: We transfected the diced small interference RNA into SiHa cells and detected cell differentiation and proliferation by immunocytochemistry, Western blot, and methyl thiazolyl tetrazolium assay.

Results: Knockdown of Hes1 and Hes5 would up-regulate the downstream gene Hash1, but not the upstream gene Notch1 in the Notch-Hes-Hash pathway. After Hes1/Hes5 RNA interference, expression of differentiation-associated proteins (including Nanog, stage-specific embryonic antigen 4, and tumor rejection antigen-1-60) was reduced, and the cell differentiation was promoted; meanwhile, the cell proliferation was inhibited, which was verified by detecting proliferation-associated proteins (eg, Ki-67, proliferating cell nuclear antigen) and methyl thiazolyl tetrazolium assay.

Conclusions: Our findings suggest that Hes1/Hes5 gene would inhibit the cell differentiation via down-regulating Hash1 and promote the cell proliferation in cervical carcinoma cells; the cell differentiation and proliferation can be reversed simultaneously by Hes1/Hes5 knockdown using RNA interference.

  • Hes1/Hes5
  • Differentiation
  • Proliferation
  • Cervical carcinoma

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Footnotes

  • This project was supported by funds from the Zhejiang Natural Science Foundation of China (Y204049, X206961, and Y2090355), the Specialized Research Fund for the Doctoral Program of Higher Education (20090101120134), and the Health Bureau of Zhejiang, China (2006QN018).

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