PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Mrna Decay Analysis in Drosophila Melanogaster: Drug-Induced Changes in Glutathione S-Transferase D21 Mrna Stability(Academic Press Inc., 2008) Akgül, Bünyamin; Tu, Chen-Pei D.We have established an in vivo system to investigate mechanisms by which pentobarbital (PB), a psychoactive drug with a sedative effect, changes the rate of decay of gstD21 mRNA (encoding a Drosophila glutathione S-transferase). Here we describe methods for the use of hsp70 promoter-based transgenes and transgenic lines to determine mRNA half-lives by RNase protection assays in Drosophila. We are able to identify and map putative decay intermediates by cRT-PCR and DNA sequencing of the resulting clones. Our results indicate that the 3′-UTR of gstD21 mRNA is responsive to PB by regulating mRNA decay and that the cis-acting element(s) responsible for the PB-mediated stabilization resides in a 59 nucleotide sequence in the 3′-UTR of the gstD21 mRNA (Akgül and Tu, 2007).Article Citation - WoS: 19Citation - Scopus: 29One Step Forward, Two Steps Back; Xeno-Micrornas Reported in Breast Milk Are Artifacts(Public Library of Science, 2016) Bağcı, Caner; Allmer, JensBackground: MicroRNAs (miRNAs) are short RNA sequences that guide post-transcriptional regulation of gene expression via complementarity to their target mRNAs. Discovered only recently, miRNAs have drawn a lot of attention. Multiple protein complexes interact to first cleave a hairpin from nascent RNA, export it into the cytosol, trim its loop, and incorporate it into the RISC complex which is important for binding its target mRNA. This process works within one cell, but circulating miRNAs have been described suggesting a role in cell-cell communication. Motivation: Viruses and intracellular parasites like Toxoplasma gondii use miRNAs to manipulate host gene expression from within the cellular environment. However, recent research has claimed that a rice miRNA may regulate human gene expression. Despite ongoing debates about these findings and general reluctance to accept them, a recent report claimed that foodborne plant miRNAs pass through the digestive tract, travel through blood to be incorporated by alveolar cells excreting milk. The miRNAs are then said to have some immunerelated function in the newborn. Principal Findings: We acquired the data that supports their claim and performed further analyses. In addition to the reported miRNAs, we were able to detect almost complete mRNAs and found that the foreign RNA expression profiles among samples are exceedingly similar. Inspecting the source of the data helped understand how RNAs could contaminate the samples. Conclusion: Viewing these findings in context with the difficulties foreign RNAs face on their route into breast milk and the fact that many identified foodborne miRNAs are not from actual food sources, we can conclude beyond reasonable doubt that the original claims and evidence presented may be due to artifacts. We report that the study claiming their existence is more likely to have detected RNA contamination than miRNAs.Article Citation - WoS: 19Citation - Scopus: 19Irf6 Is Involved in the Regulation of Cell Proliferation and Transformation in Mcf10a Cells Downstream of Notch Signaling(Public Library of Science, 2015) Zengin, Talip; Ekinci, Burcu; Küçükköse, Cansu; Yalçın Özuysal, ÖzdenIRF6, a member of Interferon Regulatory Factors (IRF) family, is involved in orofacial and epidermal development. In breast cancer cell lines ectopic expression of IRF6 reduces cell numbers suggesting a role as negative regulator of cell cycle. IRF6 is a direct target of canonical Notch signaling in keratinocyte differentiation. Notch is involved in luminal cell fate determination and stem cell regulation in the normal breast and is implicated as an oncogene in breast cancer. Notch activation is sufficient to induce proliferation and transformation in non-tumorigenic breast epithelial cell line, MCF10A. ΔNp63, which is downregulated by Notch activation in the breast, regulates IRF6 expression in keratinocytes. In this report, we investigate Notch-IRF6 and ΔNp63-IRF6 interactions in MCF10A and MDA MB 231 cells. We observed that in these cells, IRF6 expression is partially regulated by canonical Notch signaling and ΔNp63 downregulation. Furthermore, we demonstrate that IRF6 abrogation impairs Notch-induced proliferation and transformation in MCF10A cells. Thus, we confirm the previous findings by showing a tissue independent regulation of IRF6 by Notch signaling, and extend them by proposing a context dependent role for IRF6, which acts as a positive regulator of proliferation and transformation in MCF10A cells downstream of Notch signaling.Article Citation - WoS: 10Citation - Scopus: 10High-Copy Overexpression Screening Reveals Pdr5 as the Main Doxorubicin Resistance Gene in Yeast(Public Library of Science, 2015) Demir, Ayşe Banu; Koç, AhmetDoxorubicin is one of the most potent anticancer drugs used in the treatment of various cancer types. The efficacy of doxorubicin is influenced by the drug resistance mechanisms and its cytotoxicity. In this study, we performed a high-copy screening analysis to find genes that play a role in doxorubicin resistance and found several genes (CUE5, AKL1, CAN1, YHR177W and PDR5) that provide resistance. Among these genes, overexpression of PDR5 provided a remarkable resistance, and deletion of it significantly rendered the tolerance level for the drug. Q-PCR analyses suggested that transcriptional regulation of these genes was not dependent on doxorubicin treatment. Additionally, we profiled the global expression pattern of cells in response to doxorubicin treatment and highlighted the genes and pathways that are important in doxorubicin tolerance/toxicity. Our results suggest that many efflux pumps and DNA metabolism genes are upregulated by the drug and required for doxorubicin tolerance.Article Citation - WoS: 13Citation - Scopus: 13Stat Pathway in the Regulation of Zoledronic Acid-Induced Apoptosis in Chronic Myeloid Leukemia Cells(Elsevier Ltd., 2013) Kiper, Hatice Demet; Tezcanlı Kaymaz, Burçin; Adan Gökbulut, Aysun; Selvi, Nur; Biray Avcı, Çığır; Kosova, Buket; İskender, Güniz; Kartal Yandım, Melis; Gündüz, Cumhur; Şahin, Fahri; Baran, Yusuf; Saydam, GürayIn this study, we aimed to evaluate the cytotoxic and apoptotic effects of zoledronic acid on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on zoledronic acid-induced apoptosis. The results showed that zoledronic acid decreased proliferation, and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT3, -5A and -5B genes were significantly reduced in zoledronic acid-treated K562 cells. These data indicated that STAT inhibition by zoledronic acid may be therapeutic in CML patients following the confirmation with clinical studies. © 2013 Elsevier Masson SAS.Article Citation - WoS: 23Citation - Scopus: 24Proteasome Inhibitor Bortezomib Increases Radiation Sensitivity in Androgen Independent Human Prostate Cancer Cells(Elsevier Ltd., 2010) Göktaş, Serdar; Baran, Yusuf; Ural, Ali Uğur; Yazıcı, Sertaç; Aydur, Emin; Başal, Şeref; Avcu, Ferit; Pekel, Aysel; Dirican, Bahar; Beyzadeoğlu, MuratObjectives: To investigate the effects of a strong proteasome inhibitor, bortezomib alone or in combination with radiotherapy on androgen-independent DU145 human prostate cancer cells. Proteasomes play important roles in cell cycle, proliferation, apoptosis, angiogenesis, and cellular resistance to chemotherapy and radiotherapy. Methods: Increasing concentrations of bortezomib alone or in combination with radiation were applied to DU145 cells and IC50 values that inhibited cell growth by 50% were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium-bromide assay. Apoptosis was determined using annexin V staining by flow cytometry. mRNA levels of proapoptotic caspase-3 and antiapoptotic Bcl-2 genes were examined by reverse transcriptase polymerase chain reaction. Results: The IC50 value of bortezomib was found to be 28 μm although 400- and 800-cGy radiation decreased the cell proliferation by 14% and 28%, respectively. In 400- and 800-cGy radiation applied DU145 cells, IC50 value of bortezomib decreased to 23- and 12 μm, respectively. Exposure to 5 μm bortezomib for 48 hours caused apoptosis in 35% of the population whereas 800-cGy radiation resulted apoptosis in 14% of cells. However, 42% of DU145 cells that were exposed to 800 cGy and 5 μm bortezomib underwent apoptosis. Reverse transcriptase polymerase chain reaction results showed a significant decrease in mRNA levels of antiapoptotic Bcl-2 gene and an increase in proapoptotic caspase-3 gene expression in the combination group compared to control group. Conclusions: Bortezomib increases radiation sensitivity in androgen-independent human DU145 prostate cancer cells through inhibition of Bcl-2 and induction of caspase-3 genes. © 2010 Elsevier Inc. All rights reserved.