Related Experiment Video
Updated: Dec 23, 2025
Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Long non-coding RNA GAS5 accelerates oxidative stress in melanoma cells by rescuing EZH2-mediated CDKN1C
Wei Xu1, Zeqiang Yan2, Fen Hu3
11Department of Dermatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021 People's Republic of China.
Background:
The significance of long non-coding RNAs (lncRNAs) in mediating oxidative stress of cancers has been implicated recently. This study proposed a potential therapeutic target lncRNA growth arrest-specific transcript 5 (GAS5) for melanoma, due to its crucial role in oxidative stress and apoptosis of melanoma cells by regulating the enhancer of zeste homolog 2 (EZH2)-mediated CDKN1C expression.
Methods:
The lncRNA GAS5 expression pattern was examined in melanoma tissues and cells. The correlation of lncRNA GAS5, EZH2, and CDKN1C with survival rate of melanoma patients was analyzed. In melanoma cell lines, lncRNA GAS5 expression was overexpressed or knocked down to clarify its effects on cell viability, apoptosis, and oxidative stress. The interaction between lncRNA GAS5 and EZH2 was examined by RIP and RNA pull-down assays followed by verification of the target relationship between EZH2 and CDKN1C.
Results:
High expression of EZH2 and poor expression of lncRNA GAS5 and CDKN1C was observed in melanoma tissues and found to be correlated with the reduction in survival expectancy of melanoma patients. Overexpression of lncRNA GAS5 or CDKN1C or EZH2 knockdown could inhibit cell viability but enhance melanoma cell apoptosis and oxidative stress. Importantly, lncRNA GAS5 attenuated EZH2 expression by recruiting E2F4 to the EZH2 promoter region and knockdown of EZH2 upregulated CDKN1C expression by inhibiting the H3K27me3.
Conclusion:
The evidence provided by our study highlighted the involvement of lncRNA GAS5 in the translational suppression of EZH2 as well as the upregulation of CDKN1C, resulting in the promotion of melanoma cell apoptosis and oxidative stress.
Insights
Long non-coding RNA GAS5 (growth arrest-specific transcript 5) promotes melanoma cell apoptosis and oxidative stress by targeting EZH2 and upregulating CDKN1C. This finding suggests GAS5 as a potential therapeutic target for melanoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer progression.
- Oxidative stress and apoptosis are critical processes in melanoma development.
Purpose of the Study:
- To investigate the role of lncRNA GAS5 (growth arrest-specific transcript 5) in melanoma.
- To explore GAS5's potential as a therapeutic target by examining its regulation of EZH2 and CDKN1C.
Main Methods:
- Assessed lncRNA GAS5 expression in melanoma tissues and cell lines.
- Correlated GAS5, EZH2, and CDKN1C levels with patient survival.
- Manipulated GAS5 expression to evaluate effects on cell viability, apoptosis, and oxidative stress.
- Investigated molecular interactions using RIP and RNA pull-down assays.
Main Results:
- Melanoma tissues showed high EZH2 and low GAS5/CDKN1C expression, correlating with reduced survival.
- GAS5 overexpression or EZH2 knockdown inhibited cell viability while enhancing apoptosis and oxidative stress.
- GAS5 suppressed EZH2 expression by recruiting E2F4 to the EZH2 promoter.
- EZH2 knockdown upregulated CDKN1C via H3K27me3 inhibition.
Conclusions:
- lncRNA GAS5 promotes melanoma cell apoptosis and oxidative stress.
- GAS5 functions by translationally suppressing EZH2 and upregulating CDKN1C.
- GAS5 represents a promising therapeutic target for melanoma.
Related Concept Videos
02:36DNA Damage can Stall the Cell Cycle
02:36DNA Damage Can Stall the Cell Cycle
02:23Abnormal Proliferation
02:31Nuclear Export of mRNA
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...