Moleküler Biyoloji ve Genetik Bölümü Makale Koleksiyonu

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https://hdl.handle.net/20.500.12713/2073

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Epibrassinolide impaired colon tumor progression and induced autophagy in SCID mouse xenograft model via acting on cell cycle progression without affecting endoplasmic reticulum stress observed in vitro
(Elsevier Ltd, 2023) Obakan Yerlikaya, Pınar; Adacan, Kaan; Karatuğ Kaçar, Ayşe; Çöker Gürkan, Ajda; Arısan, Elif Damla
Epibrassinolide is a member of brassinosteroids with a polyhydroxysteroid structure similar to steroid hormones of vertebrates. It was shown that EBR decreased cell proliferation and induced apoptosis in different colon cancer cell lines without exerting a cytotoxic effect in epithelial fetal human colon cells. This finding highlighted the potential of epibrassinolide in clinical therapeutic setup. In our previous studies, we showed that epibrassinolide was able to induce apoptosis via endoplasmic reticulum stress. Recently, we also showed that endoplasmic reticulum and apoptotic stresses can be prevented via autophagic induction in non-cancerous epithelial or aggressive forms of cancer cells. Therefore, here in this study, we evaluated the anti-tumoral effect of epibrassinolide as well as the autophagy involvement in the aggressive forms of colon cancer cell lines as well as in vivo SCID mouse xenograft colon cancer model for the first time. For this purpose, SCID mouse model was used for subcutaneous injection of colon cancer cells in matrigel formulation. We found that autophagy is induced in both in vitro and in vivo models. Following tumor formation, SCID mice were treated daily with increasing concentrations of epibrassinolide for two weeks. Our findings showed that EBR inhibited the volume and diameter of the tumor in a dose-dependent manner by causing cell cycle arrest. Therefore our data suggest that epibrassinolide exerts a cytostatic effect on the agrressive form of colon cancer model in vivo, without affecting endoplasmic reticulum stress and the induction of autophagy might have role in this effect of epibrassinolide. © 2023 Elsevier Ltd
Establishment of direct organogenesis protocol for arachis hypogaea cv. virginia in liquid medium by temporary immersion system (TIS)
(MDPI, 2022) Özüdoğru, Elif Aylin; Karlık, Elif; Elazab, Doaa; Lambardi, Maurizio
Peanuts (Arachis hypogaea L.) are a rich source of herbal oil, proteins, minerals, vitamins, fibers, essential amino acids, as well as bioactive compounds, and are thus widely used for human nutrition and animal feed, and for prevention from certain diseases. However, the in vitro regeneration response of the species is generally low, and it also displays a significant variability among its varieties. Thus, the development of advanced protocols and approaches for the in vitro propagation of peanut is still of immense importance. A recently developed in vitro propagation technique, TIS; Temporary Immersion Bioreactor System, provides a new approach for the mass propagation of plants. Accordingly, the present study provides an efficient de novo regeneration protocol for Arachis hypogaea L. cv. Virginia by using a TIS. Different concentrations of cytokinins, i.e., benzyladenine (BA) or thidiazuron (TDZ), were tested with several combinations of dry and medium immersion periods of TIS, corresponding to a total of 8, 12, 16, 24, 32, 36, 48, 64, 72, and 96 min daily immersions for the induction of direct organogenesis. The study exhibited that an MS medium added to 110 µM BA or 10 µM TDZ are the most appropriate medium formulations in TIS, when applied for 16 min every 16 h. The application of optimized procedures to cv. NC7 and two valuable Turkish autochthonous varieties, 7 × 77 and Com74, is also reported. To the best of our knowledge, the present study draws attention also for being the first study in which a TIS was used for peanuts. © 2022 by the authors.
Comparative retrotransposon analysis in wheat
(2022) Altıntaş, Seray; Ilgar, Bekir Ahmet; Karlık, Elif
The presence of retrotransposons is associated with polyploidy, especially in wheat, and may cause an increase in genome size. In this study, the evolutionary information was aimed to reveal based on the comparison retrotransposon movements between bread and einkorn wheat. For that reason, the transposition of BARE1, Sukkula and Nikita retrotransposons in bread and einkorn wheat were analysed by using IRAP-PCR molecular marker method. Both monomorphic and polymorphic bands in each wheat species have been demonstrated. IRAP-PCR products of Sukkula retrotransposon was showed as 10 bands in bread wheat, but no bands could be determined in einkorn wheat. Nikita retrotransposon was demonstrated as 6 bands in bread wheat, 14 bands in einkorn wheat. Polymorphism rate was calculated as 81% for Nikita between bread wheat and einkorn wheat. However, the presence of BARE1 were not observed in both species. The obtained findings suggest that Nikita retrotransposon contributes to genome obesity, especially in bread wheat. The failure of Sukkula retrotransposon detection in einkorn wheat indicates that Sukkula may be inserted in the genome of bread wheat by horizontal gene transfer during wheat domestication events. These results may contribute understand the organization of wheat genome during domestication.
Discussing the roles of proline and glycine from the perspective of cold adaptation in lipases and cellulases
(TAYLOR & FRANCIS, 2022) Öten, Ahmet Melih; Atak, Evren; Karaca, Banu Taktak; Fırtına, Sinem; Kutlu, Aslı
Lipases and cellulases have been extensively used in the field of biotechnology for varied purposes. Mainly, the ongoing researches focus on the improvements of kinetic and enzymatic characteristics of enzymes to meet industrial needs. With the discovery of psychrophilic cellulase and lipase sources, a new era has opened for protein research by allowing the discovery of novel functions together with the description of unique cold adaptation mechanisms to harsh environments. The ability of cold-adapted lipase and cellulases to enable chemical reactions at lower temperatures provides a great opportunity to cut the cost of the finished product by lowering energy and purifying expanses. The advances in the cold-adapted lipase and cellulase enzymes are the cumulative efforts of organic chemists, biophysicists, biotechnologists, and process engineers who greatly contribute to a better understanding of cold-adaptation phenomena from different points of view. In this review, we cover the cold-adaptation aspects of cellulase and lipase enzymes from structural points of view by referring to the roles of Gly and Pro residues. Gly and Pro residues accelerate the cold-adaptation of enzymes by altering the conformational changes in the 3 D structure of proteins The list of microorganisms as a source of cold-adapted cellulases and lipases is given by referring to biotechnological applications. After introducing the thermodynamic background of Gly and Pro residues in the phenomena of cold-adaptation, specific examples are given to emphasise how introducing Gly and Pro into 3 D structure of protein molecules adds value in terms of biotechnological application by contributing to cold-adaptation
Impact of 5HydroxyMethylCytosine (5hmC) on reverse/direct association of cell-cycle, apoptosis, and extracellular matrix pathways in gastrointestinal cancers
(Springer, 2022) Moravveji, Sayyed Sajjad; Khoshbakht, Samane; Mokhtari, Majid; Salimi, Mahdieh; Lanjanian, Hossein; Nematzadeh, Sajjad; Torkamanian-Afshar, Mahsa; Masoudi-Nejad, Ali
Background: Aberrant levels of 5-hydroxymethylcytosine (5-hmC) can lead to cancer progression. Identifcation of 5-hmC-related biological pathways in cancer studies can produce better understanding of gastrointestinal (GI) cancers. We conducted a network-based analysis on 5-hmC levels extracted from circulating free DNAs (cfDNA) in GI cancers including colon, gastric, and pancreatic cancers, and from healthy donors. The co-5-hmC network was reconstructed using the weighted-gene co-expression network method. The cancer-related modules/subnetworks were detected. Preservation of three detected 5-hmC-related modules was assessed in an external dataset. The 5-hmC-related modules were functionally enriched, and biological pathways were identifed. The relationship between modules was assessed using the Pearson correlation coefcient (p-value<0.05). An elastic network classifer was used to assess the potential of the 5-hmC modules in distinguishing cancer patients from healthy individuals. To assess the efciency of the model, the Area Under the Curve (AUC) was computed using fve-fold cross-validation in an external dataset. Results: The main biological pathways were the cell cycle, apoptosis, and extracellular matrix (ECM) organization. Direct association between the cell cycle and apoptosis, inverse association between apoptosis and ECM organiza? tion, and inverse association between the cell cycle and ECM organization were detected for the 5-hmC modules in GI cancers. An AUC of 92% (0.73–1.00) was observed for the predictive model including 11 genes. Conclusion: The intricate association between biological pathways of identifed modules may reveal the hidden signifcance of 5-hmC in GI cancers. The identifed predictive model and new biomarkers may be benefcial in cancer detection and precision medicine using liquid biopsy in the early stages.
Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug-gene interaction networks analysis
(Nature, 2022) MotieGhader, Habib; Tabrizi-Nezhadi, Parinaz; Abad Paskeh, Mahshid Deldar; Baradaran, Behzad; Mokhtarzadeh, Ahad; Hashemi, Mehrdad; Lanjanian, Hossein; Jazayeri, Seyed Mehdi; Maleki, Masoud; Khodadadi, Ehsan; Nematzadeh, Sajjad; Maghsoudloo, Mazaher; Masoudi-Nejad, Ali; Kiani, Farzad
Lung cancer is the most common cancer in men and women. This cancer is divided into two main types, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Around 85 to 90 percent of lung cancers are NSCLC. Repositioning potent candidate drugs in NSCLC treatment is one of the important topics in cancer studies. Drug repositioning (DR) or drug repurposing is a method for identifying new therapeutic uses of existing drugs. The current study applies a computational drug repositioning method to identify candidate drugs to treat NSCLC patients. To this end, at frst, the transcriptomics profle of NSCLC and healthy (control) samples was obtained from the GEO database with the accession number GSE21933. Then, the gene co-expression network was reconstructed for NSCLC samples using the WGCNA, and two signifcant purple and magenta gene modules were extracted. Next, a list of transcription factor genes that regulate purple and magenta modules’ genes was extracted from the TRRUST V2.0 online database, and the TF–TG (transcription factors–target genes) network was drawn. Afterward, a list of drugs targeting TF–TG genes was obtained from the DGIdb V4.0 database, and two drug–gene interaction networks, including drug-TG and drug-TF, were drawn. After analyzing gene co-expression TF–TG, and drug–gene interaction networks, 16 drugs were selected as potent candidates for NSCLC treatment. Out of 16 selected drugs, nine drugs, namely Methotrexate, Olanzapine, Haloperidol, Fluorouracil, Nifedipine, Paclitaxel, Verapamil, Dexamethasone, and Docetaxel, were chosen from the drug-TG sub-network. In addition, nine drugs, including Cisplatin, Daunorubicin, Dexamethasone, Methotrexate, Hydrocortisone, Doxorubicin, Azacitidine, Vorinostat, and Doxorubicin Hydrochloride, were selected from the drug-TF sub-network. Methotrexate and Dexamethasone are common in drug-TG and drug-TF sub-networks. In conclusion, this study proposed 16 drugs as potent candidates for NSCLC treatment through analyzing gene co-expression, TF–TG, and drug–gene interaction networks.
Distinctive SIRE1 retrotransposon patterns on barley chromosomes?
(DergiPark, 2021) Gözükırmızı, Nermin; Karlık, Elif
SIRE1 is an active and relatively high copy-number retroelement belongs to the Tyl/Copia long terminal repeat (LTR) retrotransposon superfamily. Distinctive SIRE1 elements (ENV and GAG) distributions in barley genome were observed by using fluorescent in situ hybridization (FISH). We performed PCR to obtain tetramethylrhodamine-dUTP (TRITC)-labelled probes. Localizations of SIRE1 ENV and GAG domains were demonstrated under confocal microscope on Hordeum vulgare L. cv. Hasat root preparations. Our results revealed the distributions of SIRE1 elements ENV and GAG in barley genome. These results may provide to uncover the organization of SIRE retrotransposon pattern in barley genome.
Why lncRNAs were not conserved? Is it for adaptation?
(TR- Dizin, 2021) Karlık, Elif
Plants are sessile organisms affected by changing environment, especially biotic and abiotic stress. Long non-coding RNAs (lncRNAs) became prominent as crucial regulators in diverse biological mechanisms, including developmental processes and stress responses such as salinity. In this study, salinity related lncRNAs were sequenced and analyzed according to homology based on rice and maize lncRNA sequences. After sequencing, 72HASATROOT and 72TARMROOT were identified as 568 bp, additionally, 72HASATSHOOT and 72TARMSHOOT were also 568 bp according to reference sequence which are the member of the naturalantisense lncRNA with 565 bp. Besides, 77HASATROOT and 77TARMROOT were identified as 676 and 644 bp, additionally, 77HASATSHOOT and 77TARMSHOOT were 666 bp according to reference sequence alignment that reference sequence was 667 bp and the sno-lncRNA member. Sequencing studies demonstrated sequence alterations resulted in secondary structure changes which may affect the adaptation of varieties in response to stress. As a conclusion, rapid evolution of lncRNAs may be another force for adaptation to changing environment in plants.
Cotton biotechnology: An efficient gene transfer protocol via agrobacterium tumefaciens for a greater transgenic recovery
(TAYLOR & FRANCIS INC, 2022)
Due to its economic worth, cotton (Gossypium hirsutum L.) is grown in almost 70 countries and provides income for more than 250 million people. Therefore, producing cotton with having some desired characteristics that includes extended biotic and abiotic stress tolerance, improved fiber quality, promoted nutritional content and increased yield is the main objective for cotton biotechnology. To achieve this goal, many tissue culture and gene transfer techniques are being developed and used throughout the years. As applications for the gene transfer, the Agrobacterium-mediated, particle bombardment and pollen tube pathway-mediated methods are most successfully used and in conjunction with this, meristematic shoot tips as explants are efficiently utilized in gene transfer methods. In this study, the main objective was to report an efficient protocol for a greater recovery of transgenic cotton plant using Agrobacterium tumefaciens-mediated transformation. For this, one of the cotton strains (Cukurova 1518) cultivated widely in Turkey was chosen and meristematic shoot tips as explant sources, and GFP and NPTII genes as reporter and marker genes were used, respectively. The effective post co-cultivation conditions were provided via using the selection regime in vitro. Finally, the current results showed highly reproducible protocol developed could be used to produce transgenic cotton plants expressing desired traits or can be utilized as a model system to study the expression of particular genes.
İnsan endojen retrovirüslerin kanserle olan ilişkisinin incelenmesi
(2022) Karaman, Abdullah; Karlık, Elif
Transpozonlar, genomdaki yerlerini değiştirebilme özelliğine sahip olan hareketli DNA parçalarıdır. Transpozonlar genomdaki yer değiştirme işlemini, transpozisyon olarak adlandırılan bir mekanizma ile gerçekleştirmekte ve sahip oldukları transpozisyon mekanizmasına göre DNA ve RNA transpozonları olarak iki alt sınıfa ayrılmaktadırlar. Retrotranspozonlar olarak da adlandırılan RNA transpozonları, insanın evrim sürecinde önemli rol alan endojen retrovirüsleri (ERV) içermektedir. İnsan genomunun yaklaşık %8’ini oluşturan insan endojen retrovirüsleri (HERV) 3 sınıf altında toplanmakta olup ikinci sınıfta yer alan insan endojen retrovirüs K (HERV-K), insan genomuna yakın sayılabilecek bir zamanda entegre olan, insan genomundaki en aktif HERV’dir. HERV-K’nın gen anlatım analizleri incelendiğinde, ovaryum, meme ve deri kanseri gibi çeşitli kanser türlerinin ortaya çıkmasında HERV-K’nın rol aldığı görülmektedir. HERV’lerin kanser gelişimi ile olan ilişkisi uzun süredir araştırılmaktadır. Kanser hücrelerinde HERV proteinleri saptanmış olsa da HERV’lerin kanser gelişimindeki rolü kesin olarak anlaşılamamıştır. Son dönemde yapılan çalışmalar kanser hücrelerinde yüksek seviyede anlatım yaptığı gösterilen HERV proteinlerinin, kanser tedavisinde rol alan immün yanıt için ana hedef olarak kullanılabileceğini ortaya koymaktadır. Histon deasetilaz inhibitörleri ve kontrol noktası inhibitörlerinin kombinasyonundan oluşan yeni yaklaşımlar da kanser tedavisinde kullanılmak üzere test edilmektedir. HERV anlatımı, interferon tip 1 yanıtını etkinleştiren, sitozoldeki tek iplikli RNA’nın kalıp tanıma reseptörlerini aktive ederek immün sistem yanıtını başlatmaktadır. Bunun sonucunda CD8 T hücreleri tarafından gerçekleştirilen kanser hücresi tanınması arttırılarak kanser gelişiminin engellenebileceği öngörülmektedir. Histon deasetilaz ve kontrol noktası inhibitörlerinin kombinasyonundan meydana gelen bu yeni yaklaşım, anti-tümör aktivitesini arttırarak kanser tedavisinde yeni bir umut oluşmasına olanak sağlayacaktır.
Determining T and B Cell development by TREC/KREC analysis in primary immunodeficiency patients and healthy controls
(WILEY, 2022) Şentürk, Gizem; Ng, Yuk Yin; Eltan, Sevgi Bilgiç; Başer, Dilek; Fırtına, Sinem
T cell receptor excision circles (TRECs) and kappa-deleting excision circles (KRECs) are DNA fragments potentially indicative of T and B cell development, respectively. Recent thymic emigrants (RTEs) are a subset of peripheral cells that may also represent thymic function. Here, we investigated TREC/KREC copy numbers by quantitative real-time PCR in the peripheral blood of patients with primary immunodeficiencies (PIDs, n = 145) and that of healthy controls (HCs, n = 86) and assessed the correlation between RTEs and TREC copy numbers. We found that TREC copy numbers were significantly lower in children and adults with PIDs (P < .0001 and P < .002, respectively) as compared with their respective age-matched HCs. A moderate correlation was observed between TREC copies and RTE numbers among children with PID (r = .5114, P < .01), whereas no significant correlation was detected between RTE values and TREC content in the HCs (r = .0205, P = .9208). Additionally, we determined TREC and KREC copy numbers in DNA isolated from the Guthrie cards of 200 newborns and showed that this method is applicable to DNA isolated from both peripheral blood samples and dried blood spots, with the two sample types showing comparable TREC and KREC values. We further showed that RTE values are not always reliable markers of T cell output. Although additional confirmatory studies with larger cohorts are needed, our results provide thresholds for TREC/KREC copy numbers for different age groups.
Multi-organs-on-chips for testing small-molecule drugs: challenges and perspectives
(MDPI, 2021) Çeçen, Berivan; Karavasili, Christina; Nazir, Mubashir; Bhusal, Anant; Doğan, Elvan
Organ-on-a-chip technology has been used in testing small-molecule drugs for screening potential therapeutics and regulatory protocols. The technology is expected to boost the development of novel therapies and accelerate the discovery of drug combinations in the coming years. This has led to the development of multi-organ-on-a-chip (MOC) for recapitulating various organs involved in the drug–body interactions. In this review, we discuss the current MOCs used in screening small-molecule drugs and then focus on the dynamic process of drug absorption, distribution, metabolism, and excretion. We also address appropriate materials used for MOCs at low cost and scale-up capacity suitable for high-performance analysis of drugs and commercial high-throughput screening platforms. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Correction to: primary antibody deficiencies in Turkey: molecular and clinical aspects
(Springer, 2021) Fırtına, Sinem; Ng, Yuk Yin; Ng, Özden H.; Kıykım, Ayça; Yücel Özek, Esra; Kara, Emine Manolya; Kaya, Ayşenur
The original published version of this article contained a mistake in one of the affiliations. The correct affiliation of author Manolya Kara (7) should read: Istinye University Faculty of Medicine, VM MedicalPark Pendik Hospital, Pediatric Infectious Diseases Clinic, Istanbul, Turkey The original article has been corrected. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.
Layered double hydroxide-based nanocomposite scaffolds in tissue engineering applications
(Royal Society of Chemistry, 2021) İzbudak, Burçin; Çeçen, Berivan; Anaya, Ingrid; Kamal Miri, Amir; Bal Öztürk, Ayça; Karaöz, Erdal
Layered double hydroxides (LDHs), when incorporated into biomaterials, provide a tunable composition, controllable particle size, anion exchange capacity, pH-sensitive solubility, high-drug loading efficiency, efficient gene and drug delivery, controlled release and effective intracellular uptake, natural biodegradability in an acidic medium, and negligible toxicity. In this review, we study potential applications of LDH-based nanocomposite scaffolds for tissue engineering. We address how LDHs provide new solutions for nanostructure stability and enhancein vivostudies' success. © The Royal Society of Chemistry 2021.
Primary antibody deficiencies in Turkey: molecular and clinical aspects
(Springer Link, 2021) Fırtına, Sinem; Ng, Yuk Yin; Ng, Ozden H.; Kiykim, Ayca; Yucel Ozek, Esra; Kara, Manolya
Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n = 4), CD40L (n = 1), ICOS (n = 1), IGHM (n = 1), and TCF3 (n = 1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2-10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.
Tumor chemosensitivity assays are helpful for personalized cytotoxic treatments in cancer patients
(MDPI, 2021) Ulukaya, Engin; Karakaş Zeybek, Didem; Dimas, Konstantinos
Tumor chemosensitivity assays (TCAs), also known as drug response assays or individualized tumor response tests, have been gaining attention over the past few decades. Although there have been strong positive correlations between the results of these assays and clinical outcomes, they are still not considered routine tests in the care of cancer patients. The correlations between the assays' results (drug sensitivity or resistance) and the clinical evaluations (e.g., response to treatment, progression-free survival) are highly promising. However, there is still a need to design randomized controlled prospective studies to secure the place of these assays in routine use. One of the best ideas to increase the value of these assays could be the combination of the assay results with the omics technologies (e.g., pharmacogenetics that gives an idea of the possible side effects of the drugs). In the near future, the importance of personalized chemotherapy is expected to dictate the use of these omics technologies. The omics relies on the macromolecules (Deoxyribonucleic acid -DNA-, ribonucleic acid -RNA-) and proteins (meaning the structure) while TCAs operate on living cell populations (meaning the function). Therefore, wise combinations of TCAs and omics could be a highly promising novel landscape in the modern care of cancer patients.
Transposons continue the amaze
(DergiPark, 2019) Gözükırmızı, Nermin
Transposable elements (TEs) were first discovered in maize plants. However, they exist almost in all species with a few exceptions (Plasmodium falciparum, Ashbya gossypii and Kluveromuyces lactis). They are the most important contributors to genome plasticity and evolution and even epigenetic genome regulation. Organisms with large genomes have high transposon percentages. For example, Arabidopsis thaliana has a genome size of 125 Mb which comprises 14% transposons, Homo sapiens (3000 Mb) 45-48.5%, and Hordeum vulgare genome (5300 Mb) has 80%. TEs are classified into two major groups based on their transposition mechanisms: Class I (RNA transposons – retrotransposons) and Class II (DNA transposons). Recent progress in whole-genome sequencing and long-read assembly have resulted in identification of unprecedentedly long transposable units spanning dozens or even hundreds of kilobases, initially in prokaryotic and more recently in eukaryotic systems. All TEs in a cell are named as transposome (mobilome), and transposomics is a new area to work with transposome. Although a number of bioinformatics softwares have recently been developed for the annotation of TEs in sequenced genomes, there are very few computational tools strictly dedicated to the identification of active TEs using genome-wide approaches. In this review article, after a brief introduction and review of the transposable elements, I discussed their effects in gene expression, evolution, recent applications and also share our research on retrotransposons with different organisms.
Prognostic evidence of LEF1 isoforms in childhood acute lymphoblastic leukemia
(WILEY, 2021) Erbilgin, Yucel; Hatırnaz Ng, Özden; Can, İsmail; Fırtına, Sinem; Küçükcankurt, Fulya; Karaman, Serap
Introduction: The lymphoid enhancer factor 1 (LEF1) is a DNA-binding transcription factor that functions in the Wnt signaling pathway. Increased LEF1 activity is associated with progression of several types of cancer including leukemia. Here, we investigated LEF1 isoform expression and genomic variations in acute lymphoblastic leukemia (ALL). Methods: LEF1 isoform expression was evaluated by quantitative real-time PCR in 87 newly diagnosed childhood ALL patients and controls. Moreover, Western blot analysis was performed for detection of LEF1 expression and the hotspot region of LEF1 was screened by deep sequencing. Results: The LEF1 mRNA expression of B cell ALL patients was higher than the controls (LEF1-total P = .011, LEF1-long P = .026). Moreover, B-ALL samples showing higher total LEF1 expression had significantly shorter relapse-free survival (P = .008) and overall survival (P = .011). Although full-length LEF1 expression was similar to the controls in T-ALL, 50% (n = 15) of the ALL patients had increased full-length LEF1 protein expression. Imbalance between short- and full-length LEF1 isoforms may lead to cell survival in ALL. Beside the LEF1 activation, LEF1 gene variations were rarely observed in our cohort. Conclusion: The results indicate that the Wnt pathway may have a pathogenic function in a group of ALL patients and high LEF1-total expression might be a marker for shorter relapse-free survival time in B cell ALL.
Endogenous retrovirus HERV-K6 and HERV-K11 polymorphisms’ analyses in head and neck squamous cell carcinoma patients
(Elsevier B.V., 2021) Karlık, Elif; Gürbüz, Orkun; Yıldız, Yemliha; Gözükırmızı, Nermin
Many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K (HML6) and HERV-K (HML2). However, there is no report showing any relation between squamous cell carcinoma of head and neck (HNSCC) and HERVs in literature. Here we report the polymorphic changes of HERV-K6 and HERV-K11 in tumor tissue samples of HNSCC patients comparing with healthy individuals. For this purpose, genomic DNAs from tumor tissue samples of 2 healthy individuals and of 8 HNSCC patients were isolated and IRAP-PCR was performed. IRAP-PCR analyses demonstrated that there were 18–73% polymorphism rates for HERV-K6 and 38–100% polymorphism rates for HERV-K11 among all the samples. There were also polymorphic changes between two control materials. Therefore, HERV-K6 polymorphisms may arise on an individual-specific basis. In the previous studies, some associations have been reported between the expression of HERVs and some cancer types or other major diseases. However, few reports have analyzed HERV-K movements among HNSCC patients. This report is the first study investigating HERV-K6 and HERV-K11 retrotransposon polymorphic changes in HNSCC patients.
The role of LncRNAs in translation
(MDPI, 2021) Karakaş Zeybek, Didem; Özpolat, Bülent
Abstract: Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and posttranslational levels. Depending on cellular location, lncRNAs are involved in a wide range of cellular functions, including chromatin modification, transcriptional activation, transcriptional interference, scaffolding and regulation of translational machinery. This review highlights recent studies on lncRNAs in the regulation of protein translation by modulating the translational factors (i.e, eIF4E, eIF4G, eIF4A, 4E-BP1, eEF5A) and signaling pathways involved in this process as wells as their potential roles as tumor suppressors or tumor promoters.

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