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Updated: Jul 20, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Knockdown of death receptor 5 antisense long noncoding RNA and cisplatin treatment modulate similar macromolecular
Dilek Cansu Gürer1, İpek Erdoğan Vatansever1, Çağatay Ceylan2
1Noncoding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir, Turkey.
Background/Aim:
Despite great progress in complex gene regulatory mechanisms in the dynamic tumor microenvironment, the potential contribution of long noncoding RNAs (lncRNAs) to cancer cell metabolism is poorly understood. Death receptor 5 antisense (DR5-AS) is a cisplatin inducible lncRNA whose knockdown modulates cell morphology. However, its effect on cell metabolism is unknown. The aim of this study is to examine metabolic changes modulated by cisplatin and DR5-AS lncRNA in HeLa cells.
Materials And Methods:
We used cisplatin as a universal cancer therapeutic drug to modulate metabolic changes in HeLa cervix cancer cells. We then examined the extent of metabolic changes by Fourier transform infrared spectroscopy (FTIR). We also performed transcriptomics analyses by generating new RNA-seq data with total RNAs isolated from cisplatin-treated HeLa cells. Then, we compared cisplatin-mediated transcriptomics and macromolecular changes with those mediated by DR5-AS knockdown.
Results:
Cisplatin treatment caused changes in the unsaturated fatty acid and lipid-to-protein ratios and the glycogen content. These observations in altered cellular metabolism were supported by transcriptomics analyses. FTIR spectroscopy analyses have revealed that DR5-AS knockdown causes a 20.9% elevation in the lipid/protein ratio and a 76.6% decrease in lipid peroxidation. Furthermore, we detected a 3.42% increase in the chain length of the aliphatic lipids, a higher content of RNA, and a lower amount of glycogen indicating relatively lower metabolic activity in the DR5-AS knockdown HeLa cells. Interestingly, we observed a similar gene expression pattern under cisplatin treatment and DR5-AS knockdown HeLa cells.
Conclusion:
These results suggest that DR5-AS lncRNA appears to account for a fraction of cisplatin-mediated macromolecular and metabolic changes in HeLa cervix cancer cells.
Insights
Long noncoding RNAs (lncRNAs) impact cancer cell metabolism. This study shows that DR5-AS lncRNA influences cisplatin-induced metabolic changes in HeLa cells, affecting lipid and glycogen levels.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The role of long noncoding RNAs (lncRNAs) in cancer cell metabolism remains largely unexplored.
- Death receptor 5 antisense (DR5-AS) is a cisplatin-inducible lncRNA with unknown effects on cellular metabolism.
- Understanding lncRNA contributions to cancer metabolism is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the metabolic alterations induced by cisplatin and DR5-AS lncRNA in HeLa cervical cancer cells.
- To elucidate the specific impact of DR5-AS knockdown on cellular metabolic profiles.
- To compare the metabolic and transcriptomic changes caused by cisplatin treatment versus DR5-AS knockdown.
Main Methods:
- Utilized cisplatin as a chemotherapeutic agent to induce metabolic changes in HeLa cells.
- Employed Fourier transform infrared (FTIR) spectroscopy to quantify macromolecular and metabolic shifts.
- Conducted RNA-sequencing (RNA-seq) to analyze transcriptomic alterations in response to cisplatin and DR5-AS knockdown.
Main Results:
- Cisplatin treatment altered lipid-to-protein ratios, unsaturated fatty acid content, and glycogen levels.
- DR5-AS knockdown significantly increased the lipid/protein ratio and decreased lipid peroxidation.
- DR5-AS knockdown led to increased RNA content and decreased glycogen, indicating reduced metabolic activity, with gene expression patterns mirroring cisplatin treatment.
Conclusions:
- DR5-AS lncRNA contributes to a portion of the metabolic and macromolecular changes observed following cisplatin treatment in HeLa cells.
- DR5-AS plays a role in regulating cancer cell metabolism, offering potential as a therapeutic target.
- The similar gene expression patterns suggest a functional link between DR5-AS and cisplatin's effects on cellular metabolism.
