Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Review Citation - WoS: 9Citation - Scopus: 7Micrornas and Long Non-Coding Rnas as Novel Targets in Anti-Cancer Drug Development(Bentham Science Publishers, 2023) Çetinkaya, Melisa; Baran, YusufNon-coding RNAs comprise the majority of RNAs that have been transcribed from the human genome, and these non-coding RNAs have essential regulatory roles in the cellular processes. They have been discovered to influence the expression of the genes, including tumor-suppressive and oncogenes, that establish the non-coding RNAs as novel targets for anti-cancer drug development. Among non-coding RNAs, microRNAs have been extensively studied in terms of cancer biology, and some microRNA-based therapeutics have been reached in clinical studies. Even though most of the research regarding targeting non-coding RNAs for anti-cancer drug development focused on microRNAs, long non-coding RNAs have also started to gain importance as potential therapeutic targets for cancer therapy. In this chapter, the strategies and importance of targeting microRNAs and long non-coding RNAs will be described, along with the clinical studies that involve microRNA-based cancer therapeutics and preclinical studies that involve long non-coding RNA-based therapeutics. Finally, the delivery strategies that have great importance in the effective delivery of the non-coding RNA-based cancer therapeutics, hence the therapy's effectiveness, will be described.Review Citation - WoS: 8Citation - Scopus: 8Long Noncoding Rnas in Human Cancer and Apoptosis(Bentham Science Publishers, 2023) Erdoğan, İpek; Sweef, Osama; Akgül, BünyaminGenome 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.Article Citation - WoS: 24Citation - Scopus: 29Il-17, Il-21, and Il-22 Cytokines of T Helper 17 Cells in Cancer(Mary Ann Liebert, 2019) Nalbant, AytenCD4(+) T helper (Th) cells are important regulators of cellular immune response. Newly discovered interleukin (IL)-17-producing CD4(+) T cells are known as T helper 17 cells (Th17). They are distinct subset from the T helper type 1 (Th1) and 2 (Th2) lineages. The differentiation of Th17 cells has been intensively studied; however, the role of Th17 cells in different diseases including cancer is still under investigation. Besides IL-17 family cytokines, Th17 cells produce IL-22, IL-21, and IL-26. The dysregulated function of Th17 cells and their cytokines could contribute to pathology of diseases, including cancer. The role of cytokines of Th17 cells such as IL-17, IL-21, and IL-22 in cancer will be discussed in this review.Article Citation - WoS: 278Citation - Scopus: 295Molecular Mechanisms of Drug Resistance and Its Reversal in Cancer(Taylor and Francis Ltd., 2016) Kartal Yandım, Melis; Adan Gökbulut, Aysun; Baran, YusufChemotherapy is the main strategy for the treatment of cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance. The resistance can be intrinsic or acquired. The resistance phenotype is associated with the tumor cells that gain a cross-resistance to a large range of drugs that are structurally and functionally different. Multidrug resistance arises via many unrelated mechanisms, such as overexpression of energy-dependent efflux proteins, decrease in uptake of the agents, increase or alteration in drug targets, modification of cell cycle checkpoints, inactivation of the agents, compartmentalization of the agents, inhibition of apoptosis and aberrant bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and molecular and biochemical approaches to overcome multidrug resistance have been a major goal in cancer research. This review comprises the mechanisms guiding multidrug resistance in cancer chemotherapy and also touches on approaches for reversing the resistance.Article Citation - WoS: 20Citation - Scopus: 17Differentiation of Normal and Cancer Cell Adhesion on Custom Designed Protein Nanopatterns(American Chemical Society, 2015) Horzum, Utku; Özdil, Berrin; Pesen Okvur, DevrimCell adhesion to the extracellular matrix is deregulated in metastasis. However, traditional surfaces used to study cell adhesion do not faithfully mimic the in vivo microenvironment. Electron beam lithography (EBL) is able to generate customized protein nanopatterns. Here, we used an EBL-based green lithography approach to fabricate homogeneous and gradient, single (fibronectin, K-casein) and double (fibronectin, laminin) active component protein nanopatterns with micrometer scale spacing to investigate differences in adhesion of breast cancer cells (BCC) and normal mammary epithelial cells (NMEC). Our results showed that as expected, in contrast to NMEC, BCC were plastic: they tolerated nonadhesion promoting regions, adapted to flow and exploited gradients better. In addition, the number of focal adhesions but not their area appeared to be the dominant parameter for regulation of cell adhesion. Our findings also demonstrated that custom designed protein nanopatterns, which can properly mimic the in vivo microenvironment, enable realistic distinction of normal and cancerous cell adhesion.Article Citation - WoS: 27Citation - Scopus: 27New Indication for Therapeutic Potential of an Old Well-Known Drug (propranolol) for Multiple Myeloma(Springer Verlag, 2013) Kozanoğlu, İlknur; Kartal Yandım, Melis; Çinçin, Zeynep Birsu; Özdoğu, Hakan; Çakmakoğlu, Bedia; Baran, YusufPurpose: Propranolol, a non-selective β-adrenergic receptor blocker, has been used for the treatment of the patients with hypertension for more than 50 years. There are several in vitro and in vivo evidences that β-adrenergic receptor antagonists inhibit proliferation and angiogenesis and also increase apoptosis in breast, skin, and colon cancers. The aim of this study was to investigate the cytotoxic and apoptotic effects of propranolol and the genes involved in propranolol-induced apoptosis in multiple myeloma cells. Methods: Time-dependent antiproliferation and apoptotic effects of propranolol were subsequently determined by MTT cell proliferation assay, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and also the localization of phosphatidylserine in the plasma membrane. Changes in expression levels of NF-ΚB pathway were examined by qRT-PCR array. Results: IC50 values of propranolol on U266 cells were calculated as 141, 100, and 75 μM after 24-, 48-, and 72-h propranolol exposure, respectively. There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to propranolol in U266 cells in a time- and dose-dependent manner. There were increases in expression levels of BCL10, TRAF family members, interleukins, TLR1-4, TNFRSF10B, NF-κB, and the inhibitors of NF-κB genes, and significant decreases in expression levels of Bcl-2 in response to propranolol treatment were observed. Conclusion: These results revealed that propranolol has antiproliferative and apoptotic effects on multiple myeloma cells. Being supported with in vivo analyses, propranolol can be a good and economical way to treat multiple myeloma patients.Article Citation - WoS: 42Citation - Scopus: 46Novel Agents Targeting Bioactive Sphingolipids for the Treatment of Cancer(Bentham Science Publishers, 2013) Adan Gökbulut, Aysun; Kartal Yandım, Melis; İskender, Güniz; Baran, YusufSphingolipids are a class of lipids that have important functions in a variety of cellular processes such as, differentiation, proliferation, senescence, apoptosis and chemotherapeutic resistance. The most widely studied bioactive shingolipids include ceramides, dihydroceramide (dhCer), ceramide-1-phosphate (C1P), glucosyl-ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P). Although the length of fatty acid chain affects the physiological role, ceramides and sphingosine are known to induce apoptosis whereas C1P, S1P and GluCer induce proliferation of cells, which causes the development of chemoresistance. Previous studies have implicated the significance of bioactive shingolipids in oncogenesis, cancer progression and drug- and radiation-resistance. Therefore, targeting the elements of sphingolipid metabolism appears important for the development of novel therapeutics or to increase the effectiveness of the current treatment strategies. Some approaches involve the development of synthetic ceramide analogs, small molecule inhibitors of enzymes such as sphingosine kinase, acid ceramidase or ceramide synthase that catalyze ceramide catabolism or its conversion to various molecular species and S1P receptor antagonists. These approaches mainly aim to up-regulate the levels of apoptotic shingolipids while the proliferative ones are down-regulated, or to directly deliver cytotoxic sphingolipids like short-chain ceramide analogs to tumor cells. It is suggested that a combination therapy with conventional cytotoxic approaches while preventing the conversion of ceramide to S1P and consequently increasing the ceramide levels would be more beneficial. This review compiles the current knowledge about sphingolipids, and mainly focuses on novel agents modulating sphingolipid pathways that represent recent therapeutic strategies for the treatment of cancer. © 2013 Bentham Science Publishers.