RNAi-mediated silencing of leptin gene expression increases cell death in C6 glioblastoma cells
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Updated: Aug 17, 2026

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Published on: February 13, 2013
Russell Brown1, Barbara Morash, Ehud Ur
1Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3K 6R8.
Abstract:
We previously demonstrated that the brain, pituitary, and C6 glioblastoma cells express leptin. To determine the physiological role of brain-derived leptin, we sought to selectively silence its expression using RNA interference (RNAi) in vitro. One of four potential targets, siRNA L7, reduced leptin mRNA by 50% (P < 0.05) and protein by 55% (P < 0.0001) in C6 cells. RNAi also induced a twofold increase in cell death as seen by ethidium homodimer-1 (P < 0.015) and TUNEL (P < 0.005) staining. These data suggest that endogenous leptin may be a critical factor promoting cell survival in the brain.
Insights
Endogenous leptin, a hormone found in the brain, plays a crucial role in cell survival. Silencing leptin expression in C6 glioblastoma cells using RNA interference (RNAi) significantly increased cell death, highlighting leptin's survival-promoting function.
Area of Science:
- Neuroscience
- Molecular Biology
- Cancer Research
Background:
- The brain, pituitary gland, and C6 glioblastoma cells express the hormone leptin.
- The physiological role of brain-derived leptin remains largely undetermined.
- Leptin's function in cell survival within the brain requires further investigation.
Purpose of the Study:
- To investigate the physiological role of endogenous leptin in the brain.
- To selectively silence leptin expression in C6 glioblastoma cells using RNA interference (RNAi).
- To determine the impact of leptin silencing on cell survival and cell death.
Main Methods:
- Utilized RNA interference (RNAi) with small interfering RNA (siRNA L7) to target and reduce leptin expression in vitro.
- Quantified leptin mRNA and protein levels following siRNA L7 treatment.
- Assessed cell death using ethidium homodimer-1 and TUNEL staining.
Main Results:
- siRNA L7 significantly reduced leptin mRNA by 50% (P < 0.05) and protein by 55% (P < 0.0001) in C6 cells.
- Leptin silencing via RNAi induced a twofold increase in cell death.
- Ethidium homodimer-1 and TUNEL staining confirmed significant increases in cell death (P < 0.015 and P < 0.005, respectively).
Conclusions:
- Endogenous leptin is a critical factor promoting cell survival in the brain.
- Leptin plays a significant role in maintaining the viability of C6 glioblastoma cells.
- Targeting leptin signaling could represent a potential therapeutic strategy for brain cancers.
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