Browsing by Author "Erdogan, Ipek"

Now showing 1 - 7 of 7

Citation Count: 5
Deep sequencing reveals two jurkat subpopulations with distinct miRNA profiles during camptothecin-induced apoptosis
(Tubitak Scientific & Technological Research Council Turkey, 2018) Erdogan, Ipek; Cosacak, Mehmet Ilyas; Nalbant, Ayten; Akgul, Bunyamin; Akgül, Bünyamin
MicroRNAs (miRNAs) are small noncoding RNAs of about 19-25 nt that regulate gene expression posttranscriptionally under various cellular conditions, including apoptosis. The miRNAs involved in modulation of apoptotic events in T cells are partially known. However, heterogeneity associated with cell lines makes it difficult to interpret gene expression signatures, especially in cancer-related cell lines. Treatment of the Jurkat T-cell leukemia cell line with the universal apoptotic drug, camptothecin, resulted in identification of two Jurkat subpopulations: one that is sensitive to camptothecin and another that is rather intrinsically resistant. We sorted apoptotic Jurkat cells from nonapoptotic ones prior to profiling miRNAs through deep sequencing. Our data showed that a total of 184 miRNAs were dysregulated. Interestingly, the apoptotic and nonapoptotic subpopulations exhibited distinct miRNA expression profiles. In particular, 6 miRNAs were inversely expressed in these two subpopulations. The pyrosequencing results were validated by real-time qPCR. Altogether, these results suggest that miRNAs modulate apoptotic events in T cells and that cellular heterogeneity requires careful interpretation of miRNA expression profiles obtained from drug-treated cell lines.
Citation Count: 10
Intracytoplasmic Re-localization of miRISC Complexes
(Frontiers Media Sa, 2018) Akgul, Bunyamin; Erdogan, Ipek; Akgül, Bünyamin
MicroRNAs (miRNAs) are a conserved class of non-coding RNAs of 22 nucleotides that post-transcriptionally regulate gene expression through translational repression and/or mRNA degradation. A great progress has been made regarding miRNA biogenesis and miRNA-mediated gene regulation. Additionally, an ample amount of information exists with respect to the regulation of miRNAs. However, the cytoplasmic localization of miRNAs and its effect on gene regulatory output is still in progress. We provide a current review of the cytoplasmic miRNA localization in metazoans. We then discuss the dynamic changes in the intracytoplasmic localization of miRNAs as a means to regulate their silencing activity. We then conclude our discussion with the potential molecules that could modulate miRNA localization.
Citation Count: 5
Long Noncoding RNAs in Human Cancer and Apoptosis
(Bentham Science Publ Ltd, 2023) Erdogan, Ipek; Sweef, Osama; Akgul, Bunyamin; Akgül, Bünyamin
Genome annotations have uncovered the production of at least one transcript from nearly all loci in the genome at some given time throughout the development. Surprisingly, many of these transcripts do not code for proteins and are relatively long in size, thus called long noncoding RNAs (lncRNAs). Next- and third-generation sequencing technologies have amassed numerous lncRNAs expressed under different phenotypic conditions, yet many remain to be functionally characterized. LncRNAs regulate gene expression by functioning as scaffold, decoy, signaling, and guide molecules both at the transcriptional and post-transcriptional levels, interacting with different types of macromolecules, such as proteins, DNA, and RNA. Here, we review the potential regulatory role of lncRNAs in apoptosis and cancer as some of these lncRNAs may have the diagnostic and therapeutic potential in cancer.
Citation Count: 3
Noncoding RNAs in apoptosis: identification and function
(Tubitak Scientific & Technological Research Council Turkey, 2022) Tuncel, Ozge; Kara, Merve; Yaylak, Bilge; Erdogan, Ipek; Akgul, Bunyamin; Akgül, Bünyamin
Apoptosis 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.
Citation Count: 3
Small RNA data set that includes tRNA-derived fragments from Jurkat cells treated with camptothecin
(Elsevier Science Bv, 2018) Cosacak, Mehmet Ilyas; Erdogan, Ipek; Nalbant, Ayten; Akgul, Bunyamin; Akgül, Bünyamin
In this article, we report a small RNA data set obtained from human T cell acute leukemia Jurkat cells, which were treated with the universal apoptotic agent camptothecin. Based on the Annexin-V labeling pattern, we sorted two Jurkat subpopulations in treated cells: one that is sensitive to the drug and the other being relatively more resistant. We report new original data that include the frequency of tRNA-derived fragments (tRF) in drug-sensitive and resistant cells. We also present partially analyzed data to show the origin of reads on tRNAs as well as the borders of the fragments. We believe that this data can benefit the science community working in the field of tRF and/or apoptosis. (C) 2018 The Authors. Published by Elsevier Inc.
Citation Count: 6
Transcriptomics Analysis of Circular RNAs Differentially Expressed in Apoptotic HeLa Cells
(Frontiers Media Sa, 2019) Yaylak, Bilge; Erdogan, Ipek; Akgul, Bunyamin; Akgül, Bünyamin
Apoptosis is a form of regulated cell death that plays a critical role in survival and developmental homeostasis. There are numerous reports on regulation of apoptosis by protein-coding genes as well as small non-coding RNAs, such as microRNAs. However, there is no comprehensive investigation of circular RNAs (circRNA) that are differentially expressed under apoptotic conditions. We have performed a transcriptomics study in which we first triggered apoptosis in HeLa cells through treatment with four different agents, namely cisplatin, doxorubicin, TNF-alpha and anti-Fas mAb. Total RNAs isolated from control as well as treated cells were treated with RNAse R to eliminate the linear RNAs. The remaining RNAs were then subjected to deep-sequencing to identify differentially expressed circRNAs. Interestingly, some of the dys-regulated circRNAs were found to originate from protein-coding genes well-documented to regulate apoptosis. A number of candidate circRNAs were validated with qPCR with or without RNAse R treatment as well. We then took advantage of bioinformatics tools to investigate the coding potential of differentially expressed RNAs. Additionally, we examined the candidate circRNAs for the putative miRNA-binding sites and their putative target mRNAs. Our analyses point to a potential for circRNA-mediated sponging of miRNAs known to regulate apoptosis. In conclusion, this is the first transcriptomics study that provides a complete circRNA profile of apoptotic cells that might shed light onto the potential role of circRNAs in apoptosis.
Citation Count: 5
Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells
(Frontiers Media Sa, 2021) Gurer, Dilek Cansu; Erdogan, Ipek; Ahmadov, Ulvi; Basol, Merve; Sweef, Osama; Cakan-Akdogan, Gulcin; Akgul, Bunyamin; Akgül, Bünyamin
Cisplatin is a well-known cancer chemotherapeutic agent but how extensively long non-coding RNA (lncRNA) expression is modulated by cisplatin is unknown. It is imperative to employ a comprehensive approach to obtain a better account of cisplatin-mediated changes in the expression of lncRNAs. In this study, we used a transcriptomics approach to profile lncRNAs in cisplatin-treated HeLa cells, which resulted in identification of 10,214 differentially expressed lncRNAs, of which 2,500 were antisense lncRNAs. For functional analyses, we knocked down one of the cisplatin inducible lncRNAs, death receptor 5 antisense (DR5-AS) lncRNA, which resulted in a morphological change in HeLa cell shape without inducing any cell death. A second round of transcriptomics-based profiling revealed differential expression of genes associated with immune system, motility and cell cycle in DR5-AS knockdown HeLa cells. Cellular analyses showed that DR5-AS reduced cell proliferation and caused a cell cycle arrest at S and G2/M phases. Moreover, DR5-AS knockdown reduced the invasive capacity of HeLa cells in zebrafish xenograft model. These results suggest that cisplatin-mediated pleiotropic effects, such as reduction in cell proliferation, metastasis and cell cycle arrest, may be mediated by lncRNAs.