Cervical cancer is a widespread type of cancer among women worldwide, caused by an HPV virus infection. In recent years, researchers have focused on developing new targeted treatment approaches to reduce or eliminate side effects caused by standard treatment methods used in clinics. Our research aimed to investigate the p53 signaling pathways expressed in the genomic profile of HeLa and C-4 I using RNA sequencing after applying safranal. The goal is to explore the biological processes, molecular functions, and genes involved in that pathway.
To analyze the genome profile, we applied Safranal to the cervical cancer cell lines HeLa and C-4 I for 24 h. A sequencing library was created using the RNAs isolated at the end of the incubation period. After sequencing with the DNBEQ library, we analyzed p53 signaling pathways, KEGG pathways, Gene Ontology projects, cluster heat maps, and protein-protein interactions.
Based on KEGG and GO ontology, we found that safranal down-regulated p53 signaling pathway in Hela and C-4 I cells. In total, 11 and 9 genes of HeLa and C-4 I respectively are involved in this pathway. We also observed that cyclin D and cyclin E expressions were up-regulated in HeLa and C-4 I cells, which conducted cell cycle arrest in the G1 phase. We also identified the expression of CASP-8 and FAS in HeLa cells while PIG was expressed in C-4I cells, which reflected the induction of apoptosis through extrinsic and mitochondrial pathways. Furthermore, we found that safranal inhibits angiogenesis and metastasis mechanism processes based on the expressions of CD82, and PAI in HeLa cells, and BAI-1 in C-4 I cells. Additionally, the effect of safranal on DNA has been discovered through the activation of DNA damage repair mechanism. Finally, we used heat map cluster analysis to demonstrate the differential expression of genes in control and safranal-treated cells, and their functions were determined using the KEGG map.
In conclusion, these data showed that the application of safranal leads to the downregulation of p53 signaling pathway, which showed its potential anti-cancer effects on cervical cancer cell lines, HeLa and C-4 I.
Author Contributions
S.A.A.: Conceptualization, methodology, software, formal analysis, writing—original draft preparation and writing—review and editing; F.G.Ö.: validation, visualization, supervision, project administration, funding acquisition; Ö.K.B.: project administration, funding acquisition. All authors have read and agreed to the published version of the manuscript.
Funding
This study was funded by Scientific Research Projects Coordination Unit of Istanbul University. Project number: FDK-2022-38981.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
The data presented in this study are available on request from the corresponding author.
Conflicts of Interest
The authors declare no conflict of interest.
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