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SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway

Pan Xu1, Aoran Luo1, Chuan Xiong2

  • 1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.

Cancer Cell International
|January 4, 2022
PubMed
Abstract

Insights

Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) promotes hepatocellular carcinoma (HCC) progression. Inhibiting SCUBE3 halts HCC cell growth and induces cell cycle arrest, suggesting SCUBE3 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) remains a significant global health challenge.
  • Understanding the molecular mechanisms driving HCC progression is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) in hepatocellular carcinoma (HCC) progression.
  • To elucidate the underlying molecular pathways involved in SCUBE3-mediated HCC development.

Main Methods:

  • In vitro assays (MTT, colony formation, EDU, Celigo, Caspase3/7, flow cytometry) assessed SCUBE3's impact on HCC cell proliferation, apoptosis, and cell cycle.
  • An in vivo xenograft tumor model in nude mice evaluated SCUBE3's effect on HCC growth.
  • Western blotting, co-immunoprecipitation, and pathway enrichment analysis identified key molecular players and signaling cascades.

Main Results:

  • SCUBE3 expression was significantly upregulated in HCC tissues and cell lines.
  • SCUBE3 knockdown inhibited HCC cell proliferation, induced apoptosis, and caused cell cycle arrest both in vitro and in vivo.
  • SCUBE3 promotes HCC proliferation by regulating CCNE1 expression and activating the TGFβ/PI3K/AKT/GSK3β signaling pathway, with SCUBE3 binding to the TGFβRII receptor.

Conclusions:

  • SCUBE3 plays a critical role in promoting HCC development through the TGFβ/PI3K/AKT/GSK3β pathway by regulating CCNE1.
  • SCUBE3 emerges as a promising molecular target for the clinical diagnosis and treatment of HCC.
Keywords:
AKTCCNE1Cell proliferationHepatocellular carcinomaSCUBE3

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