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Published on: June 3, 2016
FoxO3a mediates transforming growth factor-beta1-induced apoptosis in FaO rat hepatoma cells
1Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Korea. bckim@kangwon.ac.kr
Abstract:
FoxO3a is a member of the forkhead box class O (FoxO) transcription factor family and an important regulator of apoptosis. This work aimed to elucidate the involvement of FoxO3a in transforming growth factor-beta1 (TGF-beta1)-induced apoptosis in FaO rat hepatoma cells. TGF-beta1 caused a time-dependent activation of FoxO3a and a subsequent increase in FoxO response-element-containing luciferase reporter activity, which was Akt-sensitive. The FaO cells stably transfected with a wild type FoxO3a were more susceptible to the formation of apoptotic bodies, populations of sub-G1 apoptotic cells, and collapse of the mitochondrial-membrane potential triggered by TGF-beta1. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-beta1. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-beta1 signaling pathway leading to apoptosis.
Insights
Forkhead box O3a (FoxO3a) mediates transforming growth factor-beta1 (TGF-beta1)-induced apoptosis in rat hepatoma cells. This study reveals FoxO3a
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- FoxO3a is a key regulator of apoptosis within the forkhead box O transcription factor family.
- Transforming growth factor-beta1 (TGF-beta1) is implicated in various cellular processes, including apoptosis.
Purpose of the Study:
- To investigate the role of FoxO3a in TGF-beta1-induced apoptosis in FaO rat hepatoma cells.
- To elucidate the signaling pathway involving FoxO3a and TGF-beta1.
Main Methods:
- Utilized luciferase reporter assays to measure FoxO activity.
- Employed stable transfection with wild-type FoxO3a and small-interfering RNA (siRNA) for FoxO3a.
- Assessed apoptosis markers including apoptotic bodies, sub-G1 cell populations, mitochondrial membrane potential, and caspase activation.
Main Results:
- TGF-beta1 treatment led to time-dependent activation of FoxO3a and increased FoxO reporter activity, sensitive to Akt.
- Overexpression of FoxO3a enhanced susceptibility to TGF-beta1-induced apoptosis.
- Knockdown of FoxO3a using siRNA significantly inhibited TGF-beta1-induced caspase activation.
Conclusions:
- FoxO3a plays a critical role in mediating TGF-beta1-induced apoptosis in FaO rat hepatoma cells.
- FoxO3a is a crucial component of the TGF-beta1 signaling pathway that triggers apoptosis.
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