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SENP2 Reduces Hepatocellular Carcinoma Stemness and Improves Sorafenib Sensitivity Through Inactivating the

Xiaohui Tang1, Bohao Liu1, Chen Zhang1

  • 1Department of Pharmacy, Hunan Normal University School of Medicine, Changsha, China.

Frontiers in Oncology
|December 24, 2021
PubMed
Abstract

Insights

Small ubiquitin-like modifier specific peptidase 2 (SENP2) suppresses hepatocellular carcinoma (HCC) stemness and enhances sorafenib sensitivity. This occurs by inhibiting the AKT/GSK3β/CTNNB1 pathway, offering a potential therapeutic target for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hepatology

Background:

  • Small ubiquitin-like modifier specific peptidase 2 (SENP2) is implicated in various cancers, but its role in hepatocellular carcinoma (HCC) remains understudied.
  • Investigating SENP2's function in HCC is crucial for understanding cancer progression and chemoresistance.

Purpose of the Study:

  • To evaluate the effect of SENP2 on stemness and sorafenib sensitivity in HCC.
  • To elucidate the downstream signaling pathway regulated by SENP2 in HCC.
  • To validate the molecular mechanisms through compensation experiments.

Main Methods:

  • SENP2 expression was modulated using plasmid transfection.
  • Stemness was assessed via CD133+ cell proportion and sphere formation assays.
  • Sorafenib sensitivity was determined using cell counting kit-8 assays, with pathway analysis involving AKT activation and CTNNB1 overexpression.

Main Results:

  • SENP2 expression was significantly decreased in HCC cell lines, particularly in HCC stem cells.
  • SENP2 overexpression inhibited stemness markers (CD133+, sphere formation) and increased sorafenib sensitivity.
  • Compensation experiments confirmed that SENP2 suppresses HCC stemness and enhances sorafenib sensitivity by inactivating the AKT/GSK3β/CTNNB1 pathway.

Conclusions:

  • SENP2 acts as a tumor suppressor in HCC by inhibiting cancer stemness.
  • SENP2 enhances sensitivity to sorafenib, a key therapeutic agent for HCC.
  • The AKT/GSK3β/CTNNB1 signaling pathway is a critical downstream mediator of SENP2's effects in HCC.
Keywords:
AKT/GSK3β/CTNNB1 pathwaySENP2hepatocellular carcinomasorafenib sensitivitystemness

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