Epigenetic knockdown of Notch1 inhibits hepatitis B virus X protein‑induced hepatocarcinogenesis of L02/HBx cells

  • Authors:
    • Yan Peng
    • Dejiang Zhou
    • Yusheng Ye
    • Chang Kai
    • Zhongyong Jiang
    • Ziyi Zhu
    • Xiaoling Wu
    • Jie Xiong
  • View Affiliations

  • Published online on: November 15, 2018     https://doi.org/10.3892/or.2018.6867
  • Pages: 1151-1159
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Abstract

The present study aimed to investigate the effects of Notch1 on the development of hepatitis B virus X protein (HBx)‑induced hepatocarcinogenesis. The L02/HBx cells were transfected with a short hairpin RNA (shRNA) specially targeting Notch1 (Notch1‑shRNA). The mRNA and protein expression levels of Notch1 signaling pathway‑related molecules (Notch1, Hes1 and NICD) were detected after knockdown of Notch1. The effects of Notch1 knockdown on the proliferation was analyzed by Cell Counting Kit‑8 assay, and cell cycle and apoptosis of L02/HBx cells in vitro were investigated by flow cytometry. The in vivo tumor xenograft model was established by subcutaneously injection of mice with Notch1‑shRNA or sh‑NC transfected cells. The effects of Notch1 knockdown on tumor progression in vivo were then explored by H&E staining and immunohistochemistry. The results showed that knockdown of Notch1 inhibited the activation of the Notch1 signaling pathway. In addition, decreased viability and colony formation ability of L02/HBx cells were detected along with downregulated protein expression levels of Ki‑67 and PCNA (proliferating cell nuclear antigen). In addition, knockdown of Notch1 led to L02/HBx cell cycle arrest at G0/G1 phase by decreasing the expression of cyclin D1, CDK4, E2F1 and increasing the expression of p21 and retinoblastoma gene (Rb). Moreover, knockdown of Notch1 promoted the apoptosis of L02/HBx cells by activation of caspase‑3 and caspase‑9. In vivo experiments demonstrated that knockdown of Notch1 inhibited the tumorigenicity of L02/HBx cells. Our findings revealed that inhibition of the Notch1 signaling pathway may inhibit the development of HBx‑induced hepatocellular carcinoma. Notch1 may serve as a promising therapeutic target for HCC.
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February-2019
Volume 41 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Peng Y, Zhou D, Ye Y, Kai C, Jiang Z, Zhu Z, Wu X and Xiong J: Epigenetic knockdown of Notch1 inhibits hepatitis B virus X protein‑induced hepatocarcinogenesis of L02/HBx cells. Oncol Rep 41: 1151-1159, 2019
APA
Peng, Y., Zhou, D., Ye, Y., Kai, C., Jiang, Z., Zhu, Z. ... Xiong, J. (2019). Epigenetic knockdown of Notch1 inhibits hepatitis B virus X protein‑induced hepatocarcinogenesis of L02/HBx cells. Oncology Reports, 41, 1151-1159. https://doi.org/10.3892/or.2018.6867
MLA
Peng, Y., Zhou, D., Ye, Y., Kai, C., Jiang, Z., Zhu, Z., Wu, X., Xiong, J."Epigenetic knockdown of Notch1 inhibits hepatitis B virus X protein‑induced hepatocarcinogenesis of L02/HBx cells". Oncology Reports 41.2 (2019): 1151-1159.
Chicago
Peng, Y., Zhou, D., Ye, Y., Kai, C., Jiang, Z., Zhu, Z., Wu, X., Xiong, J."Epigenetic knockdown of Notch1 inhibits hepatitis B virus X protein‑induced hepatocarcinogenesis of L02/HBx cells". Oncology Reports 41, no. 2 (2019): 1151-1159. https://doi.org/10.3892/or.2018.6867