2. Academic Validation
  3. Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma

Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma

  • Sci Rep. 2020 Mar 11;10(1):4490. doi: 10.1038/s41598-020-61402-7.
Jianhua Wu  # 1,  Kuangyuan Qiao  # 2,  Yanming Du 3,  Xiaoyun Zhang 3,  Haichao Cheng 4,  Li Peng 5,  Zhanjun Guo 6
Affiliations

Affiliations

  • 1 Animal center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China.
  • 2 Basic Medical College, Hebei Medical University, Shijiazhuang, P.R. China.
  • 3 Department of Rheumatology and Immuology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China.
  • 4 Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China.
  • 5 Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China. pengli72@sina.com.
  • 6 Department of Rheumatology and Immuology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China. zjguo5886@aliyun.com.
  • # Contributed equally.
PMID: 32161353 DOI: 10.1038/s41598-020-61402-7
Abstract

The expression of lysine methyltransferase SET8, which is involved in carcinogenesis of many types of human cancers through monomethylation of histone H4 lysine 20 (H4K20), is associated with the prognosis of hepatocellular carcinoma (HCC). We performed a functional analysis for SET8 to assess its effect on HCC progression. SET8 knockdown inhibited proliferation, migration and invasion of HCC cells. SET8 knockdown also inhibited tumour growth in a human xenograft mouse model. Overexpression of SET8 displayed the reverse effect, while treatment with the SET8 inhibitor UNC0379 produced an effect similar to SET8 knockdown. In addition, drug sensitivity testing in SET8-siRNA transfected HCC cells indicated that docetaxel inhibited cell growth dramatically, as demonstrated by the Cell Counting Kit-8 (CCK-8) assay. Furthermore, gene expression microarray analysis showed that genes altered after SET8 knockdown were clustered in pathways related to tumorigenesis and metastasis. Our data suggests that targeting SET8 for HCC therapy can inhibit the proliferation and invasion of HCC cells as well as increase their sensitivity to chemotherapy.

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