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Updated: Jun 21, 2026

Isolation of CD133+ Liver Stem Cells for Clonal Expansion
Published on: October 10, 2011
Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation
Stanley K L Ng1, Soek-Ying Neo, Yann-Wan Yap
1Singapore Immunology Network A *STAR, Singapore.
Abstract:
Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs tested against the eight known catalytic PI3K isoforms, specific ablation of class II PI3K alpha (PIK3C2alpha) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2alpha mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2alpha was markedly reduced and growth arrest was associated with increased caspase 3 levels. A small but significant difference in gene dosage and expression levels was detected between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2alpha can modulate HCC cell growth.
Insights
This study reveals that class II PI3K alpha (PIK3C2alpha) significantly impairs hepatocellular carcinoma (HCC) cell growth. Targeting PIK3C2alpha shows potential for HCC treatment by inhibiting cell proliferation and inducing apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) involves complex signaling pathway disruptions, including the phosphoinositide-3-kinase (PI3K/AKT) pathway.
- The role of specific PI3K catalytic isoforms, especially class II, in HCC proliferation remains underexplored.
Purpose of the Study:
- To investigate the function of PI3K catalytic isoforms, with a focus on class II isoforms, in regulating HCC cell proliferation.
- To determine if PIK3C2alpha plays a role in HCC growth and survival.
Main Methods:
- Utilized small interfering RNAs (siRNAs) to specifically ablate eight known catalytic PI3K isoforms in HCC cells.
- Assessed the impact of PIK3C2alpha ablation on cell growth, colony formation, and apoptosis markers (caspase 3).
- Analyzed PIK3C2alpha mRNA and protein levels, and examined gene dosage and expression in tumor versus non-tumor HCC tissues from 19 patients.
Main Results:
- Specific ablation of class II PI3K alpha (PIK3C2alpha) was most effective in impairing HCC cell growth.
- PIK3C2alpha deficiency led to reduced colony formation and growth arrest, associated with increased caspase 3 levels.
- A significant difference in PIK3C2alpha gene dosage and expression was observed between HCC tumor and non-tumor tissues.
Conclusions:
- Class II PIK3C2alpha, in addition to class I PI3Ks, can modulate hepatocellular carcinoma cell growth.
- PIK3C2alpha represents a potential therapeutic target for HCC treatment.
- This study provides novel insights into the role of PI3K class II isoforms in cancer biology.
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