OncoTargets and Therapy (Jan 2019)

Downregulation of CENPK suppresses hepatocellular carcinoma malignant progression through regulating YAP1

  • Wang J,
  • Li H,
  • Xia C,
  • Yang X,
  • Dai B,
  • Tao K,
  • Dou K

Journal volume & issue
Vol. Volume 12
pp. 869 – 882

Abstract

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Jianlin Wang,* Haimin Li,* Congcong Xia,* Xisheng Yang, Bin Dai, Kaishan Tao, Kefeng Dou Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China *These authors contributed equally to this work Background: Several studies have found that centromere protein K (CENPK) is overexpressed in several tumour types and promotes tumor progression. However, there has been little research on the role of CENPK in the progression of hepatocellular carcinoma (HCC). Materials and methods: The expression of CENPK in HCC tissues was quantified by Western blot and quantitative real-time PCR. Cells were transfected with lentiviral plasmids containing shRNA sequences targeting CENPK and YAP1 to silence the expression of CENPK and YAP1. Cell Counting Kit-8 assay, colony formation assay, wound healing assay, and transwell invasion assay were performed to evaluate cell growth, migration, and invasion of HCC cells. Tumorigenicity assay was used to detect the effect of CENPK on the growth of HCC cells. Western blot assay was performed to investigate the expression of epithelial–mesenchymal transition (EMT) markers and YAP1. Results: Compared to that in adjacent non-tumor tissues, CENPK was aberrantly upregulated in HCC tumor tissues. Furthermore, CENPK knockdown significantly inhibited proliferation, migration, invasion, and EMT progression in HCC cells. Mechanistically, we identified that YAP1 was responsible for the tumor-suppressive effects of CENPK knockdown in the HCC cells. The inhibitory effects of CENPK silencing on cell proliferation, migration, invasion, and EMT were partially reversed by the restoration of YAP1 expression. Conclusion: Our results suggested that the CENPK–YAP1–EMT axis plays a critical role in regulating HCC malignant progression, indicating the role of this axis as a potential therapeutic target for HCC. Keywords: CENPK, YAP1, proliferation, migration and invasion, EMT, HCC

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