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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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DNase1L3 suppresses hepatocellular carcinoma growth via inhibiting complement autocrine effect

Qing-Yun Chen1, Lei Li2, Da-Qin Suo2

  • 1Department of Medical Research, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Neoplasma
|February 23, 2021
PubMed

Insights

Deoxyribonuclease 1 like 3 (DNase1L3) is downregulated in hepatocellular carcinoma (HCC), correlating with poorer survival. Its restoration suppresses HCC growth by inhibiting the PI3K/AKT pathway, suggesting potential as a prognostic biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Hepatocellular carcinoma (HCC) is an aggressive cancer with limited effective treatments.
  • Deoxyribonuclease 1 like 3 (DNase1L3) expression is significantly downregulated in various gastrointestinal cancers, particularly HCC.
  • DNase1L3 downregulation is frequently observed in HCC tissues compared to normal liver tissues.

Purpose of the Study:

  • To investigate the role of DNase1L3 in hepatocellular carcinoma.
  • To determine the prognostic significance of DNase1L3 in HCC patients.
  • To elucidate the mechanism by which DNase1L3 affects HCC growth.

Main Methods:

  • Analysis of DNase1L3 expression levels in HCC tissues using tissue microarrays.
  • Statistical analysis correlating DNase1L3 expression with clinical parameters (tumor size, thrombus formation, survival).
  • Gene Ontology enrichment analysis to identify associated biological processes.
  • Experimental studies involving ectopic DNase1L3 expression and PI3K/AKT pathway assessment.

Main Results:

  • DNase1L3 expression is significantly downregulated in HCC and associated with larger tumor size, tumor thrombus formation, and poorer overall and disease-free survival.
  • DNase1L3 is functionally linked to complement activation.
  • Ectopic DNase1L3 expression suppressed HCC cell growth.
  • DNase1L3 inhibited the PI3K/AKT signaling pathway activation.

Conclusions:

  • DNase1L3 may serve as a valuable prognostic biomarker for hepatocellular carcinoma patients.
  • DNase1L3 exhibits tumor-suppressive effects in HCC by inhibiting the PI3K/AKT signaling pathway.

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