TR-Dizin
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Article Citation Count: 0Cytoplasmically localized tRNA-derived fragments inhibit translation in Drosophila S2 cells(TUBITAK, 2022) Hamid,S.M.; Akgül,B.; Akgül, Bünyamin; Moleküler Biyoloji ve Genetik Bölümü; Moleküler Biyoloji ve Genetik BölümüTransfer ribonucleic acids (tRNAs) serve not only as amino acid carriers during translation but also as a template for the biogenesis of short fragments that can regulate gene expression. Despite recent progress in the function of tRNA-derived fragments (tRFs), their intracellular localization, protein partners, and role in regulating translation are not well understood. We used synthetic tRFs to investigate their localization and function in Drosophila S2 cells. Under our experimental setting, all synthetic tRFs tested were localized at distinct sites within the cytoplasm in a similar manner in Drosophila S2 cells. Cytoplasmically-localized tRFs were positioned in close proximity to GW182 and XRN1 proteins. Functionally, tRFs, which slightly suppressed proliferation in S2 cells, inhibited translation without any major shift in the polysome profile. These results suggest that 5’-tRFs are cytoplasmically-localized and regulate gene expression through inhibition of translation in Drosophila. © TÜBİTAK.Article Citation Count: 1Investigation of Potential Anticarcinogenic Effects of Corilagin in Lung Cancer Cells(Marmara Univ, inst Health Sciences, 2019) Rencuzogullari, Cagla; Cincin, Zeynep Birsu; Iplik, Elif Sinem; Baran, Yusuf; Cakmakoglu, Bedia; Baran, YusufObjective: Lung cancer (LC) is the most extensive reason of cancer associated deaths in men and women in the world. LC categorizes into two main groups due to their molecular clinicopathological features and therapeutic responses. Non-small cell lung cancer (NSCLC) is the main subgroup that consists of nearly 85% of all lung cancer types. Corilagin, a biologically active ellagitannin, could be extracted from Phyllanthus species which are known as Chinese medicinal plant. It has been recently shown that Corilagin could exert anti-inflammatuar and antioxidative effects in different experimental cancer models. However, the molecular effects of Corilagin in NSCLC remain unclear. Methods: In this study, the antiproliferative and apoptotic effects of Corilagin were identified by WST-1 cell proliferation test, caspase-3 and mitochondrial membrane potential (MMP). Results: We found that Corilagin significiantly suppressed the proliferation of NSCLC cells. Furthermore, we also showed that Corilagin could contribute apoptosis by inducing activity of caspase-3 molecule and loss of MMP. Conclusion: Taken together, our study first showed that Corilagin could be a new treatment method for NSCLC after verifying its effects with in vivo and clinical studies.Article Citation Count: 0Knockdown of death receptor 5 antisense long noncoding RNA and cisplatin treatment modulate similar macromolecular and metabolic changes in HeLa cells(Tubitak Scientific & Technological Research Council Turkey, 2022) Gurer, Dilek Cansu; Erdogan Vatansever, Ipek; Ceylan, Cagatay; Akgul, Bunyamin; 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 and metabolic changes in HeLa cervix cancer cells.Review Citation Count: 5Multidrug resistance in chronic myeloid leukemia(Tubitak Scientific & Technological Research Council Turkey, 2014) Unlu, Miray; Kiraz, Yagmur; Kaci, Fatma Necmiye; Ozcan, Mehmet Ali; Baran, Yusuf; Baran, YusufChronic myeloid leukemia (CML) is characterized by the accumulation of Philadelphia chromosome-positive (Ph+) myeloid cells. Ph+ cells occur via a reciprocal translocation between the long arms of chromosomes 9 and 22 resulting in constitutively active Bcr-abl fusion protein. Tyrosine kinase inhibitors (TKIs) are used against the kinase activity of Bcr-abl fusion protein for the effective treatment of CML. However, the development of drug resistance, directed by different genetic mechanisms, is the major problem of clinical applications of TKIs. These mechanisms include mutations in the TKI binding site of Bcr-abl, overexpression of Bcr-abl, overexpression of ATP binding cassette transporters, aberrant ceramide metabolism, inhibition of apoptosis, and changes in expression levels of microRNAs. Recently, many studies have focused on understanding the molecular mechanisms of drug resistance in cancer while targeting therapies providing reversal of resistance. Cancer stem cells also have roles in tumor initiation, maintenance, progression, metastasis, and drug resistance. Uncovering the mechanisms of drug resistance can provide more efficient treatment of cancer since these findings may provide novel targets for a complete cure. In this review, we discuss recent findings on the mechanisms of multidrug resistance and its reversal in CML.Review Citation Count: 3Noncoding RNAs in apoptosis: identification and function(Tubitak Scientific & Technological Research Council Turkey, 2022) Tuncel, Ozge; Kara, Merve; Yaylak, Bilge; Erdogan, Ipek; Akgul, Bunyamin; Akgül, BünyaminApoptosis is a vital cellular process that is critical for the maintenance of homeostasis in health and disease. The derailment of apoptotic mechanisms has severe consequences such as abnormal development, cancer, and neurodegenerative diseases. Thus, there exist complex regulatory mechanisms in eukaryotes to preserve the balance between cell growth and cell death. Initially, protein coding genes were prioritized in the search for such regulatory macromolecules involved in the regulation of apoptosis. However, recent genome annotations and transcriptomics studies have uncovered a plethora of regulatory noncoding RNAs that have the ability to modulate not only apoptosis but also many other biochemical processes in eukaryotes. In this review article, we will cover a brief summary of apoptosis and detection methods followed by an extensive discussion on microRNAs, circular RNAs, and long noncoding RNAs in apoptosis.Article Citation Count: 0Optimization of transfection of green fluorescent protein in pursuing mesenchymal stem cells in vivo(2008) Avcu, Ferit; Baran, Yusuf; Ural, Uğur; Elçi̇, Pınar; Sarper, Meral; Baran, YusufAmaç: Yeşil floresan proteini (YFP), günümüzde hücre biyolojisi çalışmalarında tanımlayıcı gen ve hücre işaretleyici olarak kullanılmaktadır. YFP’nin oldukça önemli kullanım alanları farklı genlerin içerisine eklenerek bu genlerin farklı organizmalardaki ekspresyonlarının miktar tayininde ve canlı hücreler içerisinde işaretleyici olarak kullanılabilmesidir. Bu çalışmamızda doku tamiri amacıyla ve hayvanlara aktardığımız mezankimal kök hücrelerini (MKH) in vivo takip edebilmek amacı ile YFP genini içeren plazmid vektörünün MKH’lara aktarılmasını optimize etmeye çalıştık. Yöntem ve Gereçler: Bu amaçla YFP geni taşıyan phM-YFP plazmid vektörü ve MKH’lara plazmid vektörün aktarılması amacı ile Effectene Transfeksiyon kiti kullanılmıştır.Bulgular: Elde edilen sonuçlar, MKH’ların phM-YFP ile iki defa transfekte edilmelerinin tek bir defa transfekte edilmelerine göre daha yüksek oranda ve daha uzun süreli YFP ekspresyonu sağladığını göstermiştir.Sonuç: MKH’ların YFP ile işaretlenmesi çalışmalarında transfeksiyon kimyasallarının yeterli bir inkübasyondan sonra uzaklaştırılmasının ve transfeksiyon işleminin 48 saat arayla iki defa yapılmasının MKH’ların aktarıldığı doku veya canlılarda daha uzun süreli ve daha etkin bir şekilde takibine olanak sağlayacağı gösterilmiştir