Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 4Citation - Scopus: 4Interferon Gamma-Inducible Nampt in Melanoma Cells Serves as a Mechanism of Resistance To Enhance Tumor Growth(MDPI, 2023) Barba, Cindy; Ekiz, Hüseyin Atakan; Tang, William Weihao; Ghazaryan, Arevik; Hansen, Mason; Lee, Soh-Hyun; Voth, Warren PeterSimple Summary The tumor microenvironment is complex, with interacting immune and tumor cells. Immune cells release inflammatory cytokines, including interferons (IFNs), that drive tumor clearance. However, evidence suggests that tumor cells can also utilize IFNs to enhance growth and survival in certain cases. We demonstrate that interferon gamma (IFN gamma) mediates the metabolic reprogramming of melanoma cells by inducing the essential NAD+ salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT) gene through STAT1 binding to the NAMPT locus. NAMPT is constitutively expressed in cells during normal homeostasis. However, melanoma cells have higher energetic demands and increased NAMPT. We show that IFN gamma signaling upregulates NAMPT in melanoma cells, increasing cell proliferation and survival. Further, STAT1-inducible Nampt promotes melanoma growth in mice. We provide evidence that melanoma cells directly respond to IFN gamma-activated STAT1 by increasing Nampt, which improves their fitness during tumor immunity. Elucidating mechanisms that regulate NAMPT expression can lead to enhanced therapeutic approaches with immunotherapies that utilize IFN signaling to improve patient outcomes. (1) Background: Immune cells infiltrate the tumor microenvironment and secrete inflammatory cytokines, including interferons (IFNs), to drive antitumor responses and promote tumor clearance. However, recent evidence suggests that sometimes, tumor cells can also harness IFNs to enhance growth and survival. The essential NAD+ salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT) gene is constitutively expressed in cells during normal homeostasis. However, melanoma cells have higher energetic demands and elevated NAMPT expression. We hypothesized that interferon gamma (IFN gamma) regulates NAMPT in tumor cells as a mechanism of resistance that impedes the normal anti-tumorigenic effects of IFN gamma. (2) Methods: Utilizing a variety of melanoma cells, mouse models, Crispr-Cas9, and molecular biology techniques, we explored the importance of IFN gamma-inducible NAMPT during melanoma growth. (3) Results: We demonstrated that IFN gamma mediates the metabolic reprogramming of melanoma cells by inducing Nampt through a Stat1 binding site in the Nampt gene, increasing cell proliferation and survival. Further, IFN/STAT1-inducible Nampt promotes melanoma in vivo. (4) Conclusions: We provided evidence that melanoma cells directly respond to IFN gamma by increasing NAMPT levels, improving their fitness and growth in vivo (control n = 36, SBS KO n = 46). This discovery unveils a possible therapeutic target that may improve the efficacy of immunotherapies involving IFN responses in the clinic.Article Citation - WoS: 11Citation - Scopus: 10Redefining methods for augmenting lactic acid bacteria robustness and phenyllactic acid biocatalysis: Integration valorizes simplicity(Taylor & Francis, 2022) Meruvu, HarithaThe production of phenyllactic acid (PLA) has been reported by several researchers, but so far, no mention has been made of augmented PLA production using an orchestrated assembly of simple techniques integrated to improve lactic acid bacteria (LAB) metabolism for the same. This review summarizes sequentially tailoring LAB growth and metabolism for augmented PLA catalysis through several strategies like monitoring LAB sustenance by choosing appropriate starter PLA-producing LAB strains isolated from natural environments, with desirably fastidious growth rates, properties like acidification, proteolysis, bacteriophage-resistance, aromatic/texturing-features, etc.; entrapping chosen LAB strains in novel cryogels and/or co-cultivating two/more LAB strains to improve their biotransformation potential and promote growth dependency/sustainability; adopting adaptive evolution methods designed to improve LAB strains under selection pressure inducing desired phenotypes tolerant to stress factors like heat, salt, acid, and solvent; monitoring physico-chemical LAB fermentation factors like temperature, pH, dissolved oxygen content, enzymes, and cofactors for PLA biosynthesis; and modulating purification/downstream processes to extract substantial PLA yields. This review paper serves as a comprehensive preliminary guide that can evoke a strategic experimental plan to produce industrial-scale PLA yields using simple techniques orchestrated together in the pursuit of conserving time, effort, and resources.Data Paper Knockdown of Death Receptor 5 Antisense Long Noncoding Rna and Cisplatin Treatment Modulate Similar Macromolecular and Metabolic Changes in Hela Cells(TÜBİTAK - Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, 2022) Gürer, Dilek Cansu; Erdoğan Vatansever, İpek; Ceylan, Çağatay; Akgül, BünyaminBackground/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 ametabolic changes in HeLa cervix cancer cells.Article Citation - WoS: 15Citation - Scopus: 19Campways: Constrained Alignment Framework for the Comparative Analysis of a Pair of Metabolic Pathways(Oxford University Press, 2013) Abaka, Gamze; Bıyıkoğlu, Türker; Erten, CesimMotivation: Given a pair of metabolic pathways, an alignment of the pathways corresponds to a mapping between similar substructures of the pair. Successful alignments may provide useful applications in phylogenetic tree reconstruction, drug design and overall may enhance our understanding of cellular metabolism.Results: We consider the problem of providing one-to-many alignments of reactions in a pair of metabolic pathways. We first provide a constrained alignment framework applicable to the problem. We show that the constrained alignment problem even in a primitive setting is computationally intractable, which justifies efforts for designing efficient heuristics. We present our Constrained Alignment of Metabolic Pathways (CAMPways) algorithm designed for this purpose. Through extensive experiments involving a large pathway database, we demonstrate that when compared with a state-of-the-art alternative, the CAMPways algorithm provides better alignment results on metabolic networks as far as measures based on same-pathway inclusion and biochemical significance are concerned. The execution speed of our algorithm constitutes yet another important improvement over alternative algorithms. © The Author 2013.