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Idiopathic inflammatory myopathies (IIM) are essentially treated aiming to improve muscle function and extra muscular disease manifestations. Rituximab is potentially a glucocorticoid-sparing agent which was reviewed in multiple studies with small sample sizes due to the rarity of the disease. Higher statistical power can enhance the trustworthiness of alternative treatment modalities yielding the main objective of this study. This retrospective study was conducted at a tertiary rheumatology center. Patients were diagnosed with an idiopathic inflammatory myopathy (dermatomyositis (DM), polymyositis (PM)) and were treated with rituximab to be included in this study. Parameters of disease activity including acute phase reactants, muscle enzyme levels, and disease-specific autoantibodies were analyzed. The primary study endpoint was the improvement of the patient symptoms. The secondary endpoint was the decrease in the creatinine kinase level. The study includes 26 patients (19 DM, 7 PM). The age of diagnosis was 42.04 ± 15.22 years; the follow-up duration was 64.84 ± 71.91 months. The mean corticosteroid dose decreased from 32.895 ± 24.399 to 8.44 ± 11.29 (p

Purpose: Microdeletion on Y-chromosome is a well-known genetic cause of infertility in azoospermic and oligozoospermic men. RNA transcripts possess microRNA (miRNA) response elements (MRE) that may interact with competing endogenous RNAs (ceRNA), thus repressing their activity. MiRNAs originally targeting transcripts of genes deleted in the Y-chromosome azoospermia factor (AZF) region are expected to be oriented to binding sites of new targets. We investigated miRNAs targeting genes of each AZF locus (AZFa, AZFb, AZFb-c, and AZFc) to determine their corresponding ceRNA using in silico analysis. Methods: The miRNAs targeting most of the genes deleted in each AZF locus were identified using the miRWalk database. Twelve miRNAs exhibiting potential ceRNA activity were identified and analyzed using the ComiR database. Detected ceRNAs for each AZF locus were processed in the GeneMANIA database for interaction prediction, and the most probably interacted genes were identified. Results: RPPA2, TMED3, STX7 and ATRX, GOGLB1, KMT2C genes were found potential ceRNAs for the AZFa and AZFb regions, respectively. Furthermore, CNB5, KCNC4, NDUFS1 and TROBP, HEMK1, and ORAI2 genes were the potential ceRNAs for the partially AZFb-c-overlapped region and AZFc regions, respectively. Conclusion: Our findings suggest that AZF loci deletion may change post-transcriptional regulation of gene expression through miRNA competition.

Objective: Dysregulated microRNA signatures in different cancer types are being uncovered continually implying their significance in cancer pathogenesis. miR-1267 was not previously associated with RCC. In this study, it is aimed to obtain the expression profile of miR-1267 in patients with ccRCC and its correlation with patient parameters. Methods: Kidney Cancer cDNA Array consisting of cDNA samples obtained from healthy kidney tissues of 4 healthy individuals and tumoral kidney tissues of 5 Stage I, 5 Stage II, 3 Stage III and 2 Stage IV ccRCC patients was used. Hsa-miR-1267 and SNORD48 (as housekeeping gene) expressions were analyzed. miR-1267 expression was statistically correlated with the clinical parameters of patients. miRGator 3.0 database was used to compare miR-1267 expression patterns of different urological cancer types. Results: The expression of miR-1267 was significantly higher in male than female (p=0.027). Also, there were statistically significant increase in miR-1267 expression in stage IV when compared to stage I (p0.05). Conclusion: miR-1267 could have oncogenic function, have predictive value for RCC development and be predictive about aggressiveness in ccRCC.

Prostate cancer (PCa) is the most frequent type of cancer in men. Hypericum perforatum (H. Perforatum) extract (HPE) administration provides remarkable decrease of PCa development. H. perforatum contains 7 conserved miRNAs (Hyp-miR-156a, Hyp-miR-156b, Hyp-miR-166, Hyp-miR-390, Hyp-miR-394, Hyp-miR-396 and Hyp-miR-414) with different targets. In this study, we aimed to investigate cross-kingdom gene regulation via miRNAs of H. perforatum flower dietetically absorbed in manner of an in silico approach to define potential biomarkers for PCa. psRNATarget database was used to find human genes targeted by 7 pre-defined H. perforatum miRNAs. We defined the mostly affected gene families from these miRNAs as ZNF, TMEM, SLC and FAM gene families. GeneMANIA database was used to define the most affected genes (TMEM41B and SLC4A7) from these 7 miRNAs. cBioPortal database was used to define alteration frequencies of TMEM41B and SLC4A7 on different types of PCa and to measure the mutual interaction potency and significance of co-occurence in PCa. This analysis showed that neuroendocrine prostate cancer (NEPC) had the highest total mutation frequency (22%) of TMEM41B and SLC4A7 genes. Also, TMEM41B and SLC4A7 genes had an average 2.1% pathway change potential among all different types of PCa. Moreover, TMEM41B and SLC4A7 gene pair was found significantly co-occurrent in PCa (p 0.001). Finally, via GEPIA database, we used Spearman correlation analysis to measure the correlation degree of TMEM41B and SLC4A7 genes in PCa and found their significant correlation with PCa (p = 1.2 × 10

Gunes, Sezgin/0000-0002-3103-6482 WOS: 000465264700013 PubMed: 30862152 Background/aim: This study aimed to comparatively analyze the expression levels of the SLC1A1 gene in renal specimens from tumors and adjacent healthy kidney tissues of patients with clear cell renal cell carcinoma (ccRCC). Material and methods: Nineteen patients diagnosed with ccRCC were included in the study. The expression levels of the SLC1A1 and GAPDH genes were measured in tumor and fonnalin-fixed paraffin-embedded (FFPE) tissue specimens from the adjacent healthy kidney of each subject. Via the GEPIA database, the distribution of SLC1A1 gene expressions in ccRCC and healthy kidney tissues was obtained. The relative expression of SLC1A1 was evaluated for the association with the clinical parameters of the patients. Results: The expression of the SLC1A1 gene was significantly higher in males than females (P = 0.029). Also, there were statistically significant associations between stages II-IV and Fuhrman grades 2-4 with respect to SLC1A1 gene expression (P < 0.001 for both). Moreover, low levels of red blood cell and hemoglobin counts were significantly associated with the SLC1A1 expression (P < 0.001 and P = 0.005, respectively). The expression of the SLC1A1 gene in tumor tissues increased approximately 3 times compared with normal kidney tissues (P < 0.05). According to the GEPIA database, SLC1A1 gene expression is significantly higher in ccRCC patients than healthy persons (P = 0.01). Conclusion: The change in the expression of SLC1A1 may be crucial for ccRCC pathophysiology.

Idiopathic inflammatory myopathies (IIM) are essentially treated aiming to improve muscle function and extra muscular disease manifestations. Rituximab is potentially a glucocorticoid-sparing agent which was reviewed in multiple studies with small sample sizes due to the rarity of the disease. Higher statistical power can enhance the trustworthiness of alternative treatment modalities yielding the main objective of this study.This retrospective study was conducted at a tertiary rheumatology center. Patients were diagnosed with an idiopathic inflammatory myopathy (dermatomyositis (DM), polymyositis (PM)) and were treated with rituximab to be included in this study. Parameters of disease activity including acute phase reactants, muscle enzyme levels, and disease-specific autoantibodies were analyzed. The primary study endpoint was the improvement of the patient symptoms. The secondary endpoint was the decrease in the creatinine kinase level.The study includes 26 patients (19 DM, 7 PM). The age of diagnosis was 42.04 ± 15.22 years; the follow-up duration was 64.84 ± 71.91 months. The mean corticosteroid dose decreased from 32.895 ± 24.399 to 8.44 ± 11.29 (p 0.001). Other treatment methods were methotrexate (n = 18), intravenous immunoglobulin (IVIG) (n = 7), and cyclophosphamide (n = 2). Two patients were lost to follow-up.Rituximab is shown to be effective in treating myositis along with corticosteroids as well as a corticosteroid-sparing agent in retrospective studies and open-label clinical trials; however, lack of statistical power should be underlined. Long-term decrease in steroid use and decrease in disease activity markers hint the effective use of rituximab as a glucocorticoid-sparing agent as well as its safety with minimal side effects. Key Points • Long-term decrease in steroid use and decrease in disease activity markers hint the effective use of rituximab as a glucocorticoid-sparing agent as well as its safety with minimal side effects.

Six extracts were obtained from plant speciesHypericum perforatumL., collected at Samsun in Turkey. The aim of this study was to examine the mechanisms of the anticancer activity of these extracts. Methanol, ethyl-acetate and hexane were used as a solvents for extraction from both branch-body part of the plant (extracts 1, 2 and 3) and from plant flowers (extracts 4, 5 and 6). The cytotoxic effects of the extracts were determined against 2D and 3D cancer cell models. Cell cycle changes of treated HeLa cells were analyzed by flow cytometry. Measurements of gene and microRNA expression levels in treated HeLa cells weredone by quantitative real time PCR. Five examined extracts (2–6) exerted selective concentration-dependent cytotoxic effects on HeLa, K562, and A549 cancer cells, while the extract 1 exhibited very weak cytotoxicity. The extract 6 showed the highest intensity of cytotoxic activity. All tested extracts (2–6) demonstrated the ability to induce apoptosis in HeLa cells through activation of caspase-3. These extracts remarkably decreased gene expression levels ofMMP2,MMP9,TIMP3, andVEGFAin HeLa cells. Flower extracts might have stronger effects on miR128/193a-5p/335 level changes than branch-body extracts.Hypericum perforatumextracts exerted weaker cytotoxic effects on 3D HeLa spheroids when compared with their effects on 2D monolayer HeLa cells. Taken together, results of our research may suggest the promising anticancer properties of theHypericum perforatumextracts.

Tam Metin / Full Text Erkek infertilitesi heterojen ve multifaktöriyel etiyolojili bir bozukluktur. Son yıllarda yapılan bazı çalışmalar erkek infertilitesinin yalnızca sperm üretimindeki bir bozukluktan kaynaklanmadığı, bazı olgularda diyabet, kardiyovasküler hastalıklar ve kanser gibi sistemik bir bozukluğun bir parçası olabileceğini göstermektedir. Spermatogenez sürecindeki çok sayıdaki mitoz ve mayoz bölünmeler ve bazı çevresel faktörler, mutasyon/mutasyonlara neden olabilir ve kansere yol açabilir. Bu nedenlerle, erkek infertilitesi aslında kanser için bir erken belirteç olabilir. Bu derlemede erkek infertiltesi ve kanser arasındaki ortak genomik bulgular değerlendirildi. Male infertility is a highly heterogeneous disorder with multifactorial aetiology. Recent data have demonstrated that male infertility is not only an aberration in sperm production; however, infertility might be a part of various systemic diseases including diabetes, cardiovascular and cancer in some cases of infertility. High number of cell division by mitosis and meiosis during spermatogenesis and various environmental factors may lead to mutation/mutations result in cancer. Therefore, infertility might be an early marker for male infertility. This study reviews common genomic data regarding cancer and male infertility.

WOS: 000537582600001 PubMed: 32496656 There are many unknown aspects of the pathogenesis of renal cell carcinoma (RCC). The aim of the current study was to define new RCC-related genes and measure their associations with RCC and clinical parameters, especially platelet/lymphocyte ratio which may be an independent predictor of prognosis in patients with RCC and other forms of cancer. Via in silico analysis upon RCC-specific deleted genes in chromosome 3, four possible ceRNAs (ATXN3, ABI2, GOLGB1 and SMAD2) were identified. Then, the expression levels of these genes in tumour and adjacent healthy kidney tissues of 19 RCC patients were determined by real-time PCR. ATXN3 and GOLGB1 gene expression levels increased but ABI2 gene expression level decreased in tumour kidney tissues when compared to normal ones. ATXN3, ABI2 and GOLGB1 gene expression levels were significantly higher in Fuhrman grade 4 than other grades (P < .001). ABI2 gene expression levels were significantly associated with higher platelet/lymphocyte ratio of the patients with RCC (P < .05). ATXN3, ABI2 and GOLGB1 may predict higher RCC grades. Also, ABI2 may regulate platelet/lymphocyte ratio which may be an independent predictor of RCC and other forms of cancer. Scientific Research Projects Commission of Ondokuz Mayis UniversityOndokuz Mayis University [TIP.1904.18.002] This study has been financed by Scientific Research Projects Commission of Ondokuz Mayis University (project number: PYO. TIP.1904.18.002)

Standard cancer therapies for solid malignancies, such as chemotherapy and radiotherapy, are not target specific against cancer cells and are often not fully efficacious. Chemotherapy and radiotherapy may cause side effects, and the need to develop additional strategies for cancer treatment is urgent. MicroRNAs (miRNAs) are small non-coding RNAs with heterogeneous functions and have been described in almost every known cancer model. Besides their basic tumor-suppressive and oncogenic functions, they also have the potential to modulate chemotherapy and radiotherapy and to be manipulated with chemical compounds to make them chemically suitable for efficient delivery to cancer cells. It has been suggested that the level of expression of specific miRNAs could increase treatment efficacy by determining the stage of chemotherapy/radiotherapy sensitivity. Application of miRNAs alone or in combination with standard therapeutic strategies may significantly improve the success of cancer treatments in the future.

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, involved in the silencing of messenger RNA (mRNA) translation. The importance of miRNA signatures in disease screening, prognosis, and progression of different tumor types and subtypes is increasing. miRNA expression levels change depending on numerous factors. In this review, we are describing the circumstances under which miRNA levels can change, these are named 'levels' of heterogeneity of miRNAs. miRNAs can have oncogenic, tumor suppressive, or both roles depending on tumor type and target mRNA whose translation they silence. The expression levels of a single miRNA may vary across different cancer types and subtypes, indicating that a miRNA signature may be tissue specific. miRNA levels of expression also vary during disease formation and propagation, indicating the presence of a time profile for their expression. The complexity of the miRNA-mRNA interference network mirrors different genetic and epigenetic changes that influence miRNA and mRNA availability to each other, and hence, their binding ability. The potential role of miRNAs as biomarkers is two-fold; first, for monitoring of the phases of cancer pathogenesis, and second, to characterize the particular type/subtype of cancer. It is important that a particular miRNA should be characterized by examining as many types and subtypes of cancers as are available, as well as being extracted from different types of samples, in order to obtain a complete picture of its behavior and importance in the disease pathology.

Objectives: The objective of this study is to define novel biomarkers for gastric neoplasm (GN) via in silico analysis that takes GN-specific miRNAs, finds their combinatorial target genes (potential ceRNAs), selects ones containing T-UCR among them and potentiates their relevance with GN. Based on this study we can plan new in vitro and in vivo studies. Methods: Four miRNAs of which clinical relevances with GN were proved experimentally were exported via mirTarbase. Using the ComiR database, 1008 genes targeted by these 4 miRNAs simultaneously were identified. Genes containing T-UCR and showing potential ceRNA activity were extracted. Among GN-associated ceRNAs including T-UCR, we identified genes with significant expression differences between GN and normal stomach tissue using the GEPIA database. The statistical evaluation of the association of NFAT5 and CLK3 genes with GN was performed by Spearman correlation test in GEPIA database. Results: GN-associated ceRNAs cross-matching with genes including T-UCR in their exonic regions were NFAT5 and CLK3. We identified genes with significant expression differences between GN and normal stomach tissues among GN-associated ceRNAs including T-UCR. According to this analysis, only NFAT5 gene was significantly higher expressed in GN than in normal stomach tissue while the other didn’t show any significant differential expression pattern. NFAT5 and CLK3 genes were found to be significantly correlated with GN (p

Gunes, Sezgin/0000-0002-3103-6482; us altay, diler/0000-0002-0465-8403; abur, ummet/0000-0002-4811-9321 WOS: 000495590600059 PubMed: 31342295 Truncated KIT (tr-KIT) is an alternative variant of c-KIT protein. Previous studies have clearly documented that c-KIT was associated with various oncogenic processes in RCC. However, the biological significance of tr-KIT in RCC development and progression remains unclear. So, it was aimed to investigate the possible association between RCC and tr-KIT which is thought to activate some oncogenic pathways. In this study, Kidney Cancer cDNA Array containing a total of 48 cDNA samples from the normal kidney tissues of 9 healthy subjects and kidney tumor tissues of 10 stage-1, 5 stage-2, 13 stage-3 and 11 stage-4 RCC patients was used for gene expression analysis. Real-Time PCR method was used to measure tr-KIT/c-KIT expression ratios. tr-KIT/c-KIT expression ratio was compared between tumor and normal samples, and statistically correlated with the clinical parameters of RCC patients. tr-KIT/c-KIT expression ratio was approximately 4-times higher in tumor samples than control ones (p = 0.001). Also, tr-KIT/c-KIT expression ratio was approximately two, three and six times higher in Fuhrman nuclear grades 2, 3 and 4 than normal, respectively (p = 0.009). Moreover, clear cell and papillary RCC has a significantly higher level of tr-KIT/c-KIT expression ratio than chromophobe RCC (p = 0.016). In the current study, it was stated for the first time that tr-KIT/c-KIT expression ratio was up-regulated in RCC tissues, and high tr-KIT/c-KIT expression ratio was correlated with more aggressive clinical features and poor patient prognosis. Our results suggest that increased tr-KIT/c-KIT expression ratio might be useful as a prognostic marker for RCC patients. Scientific & Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [118S162] This study was funded by The Scientific & Technological Research Council of Turkey (TUBITAK) (Grant No: 118S162).

Objective: The objective of this study is to define novel biomarkers for Prostate Cancer (PCa) via in silico analysis that takes PCa-specific miRNAs, finds their combinatorial target genes (potential ceRNAs), selects ones containing Transcribed Ultra Conserved Region (T-UCR) among them and potentiates their relevance with PCa. Methods: Thirty-four miRNAs of which clinical relevances with PCa were proved experimentally were exported via miRWalk database.Using the ComiR database, 859 genes targeted by these 34 miRNAs simultaneously were identified. Genes with ComiR score above 0.911 were taken into account. Genes containing T-UCR and showing potential ceRNA activity were extracted. Among PCa-associated ceRNAs including T-UCR, we identified genes with significant expression differences between PCa and normal prostate tissue using the GEPIA database. The statistical evaluation of the association of NFAT5 and PTBP2 genes with PCa was performed by Spearman correlation test in GEPIA database. Results: PCa-associated ceRNAs cross-matching with genes including T-UCR in their exonic regions were NFAT5, CLK3, PTBP2, CPEB4, MIPOL1 and TCF4. We identified genes with significant expression differences between PCa and normal prostate tissues among PCa-associated ceRNAs including T-UCR. According to this analysis, NFAT5 and PTBP2 genes were significantly less expressed in PCa than in normal prostate tissue while the others didn’t show any significant differential expression pattern. NFAT5 and PTBP2 genes were found to be significantly associated with PCa (p=0.000012; R=0.72). Conclusion: All in all, this is the study associating NFAT5 and PTBP2 genes with PCa and giving them tumor suppressive potential for PCa. Still, larger and more comprehensive studies are needed on this issue.

Display OmittedPolymorphisms in miRNA genes or miRNA target sites (miRSNPs) can change miRNA activity. Many researches have revealed that SNPs in miRNA target sites improve or decrease the efficacy of the interaction between miRNAs and their target genes. Cross-matches of SNPs in the miR-339-3p and in the binding site with 5'UTR of CASP3. Our aim was to specify miRSNPs on CASP3 gene (caspase-3) and SNPs in miRNA genes targeting 5'UTR and coding exons of CASP3, and evaluate the effect of these miRSNPs and SNPs of miRNA genes with respect to apoptosis. According to dbSNP 141 database, genomic locations of SNPs found in the miR-339-3p and in the binding site with 5'UTR of CASP3 were matched with each other. Co-localizations were screened. In the binding site, miR-339-3p makes 10 base-pairings with CASP3 5'UTR. MiR-339-3p geneomic sequence has three SNPs. Two of them (rs565188493, G/A; rs72631820, A/G) were localized in the binding site on the CASP3 5'UTR and one (rs373011663, C/T) was not on the binding site on the CASP3 5'UTR. Also, CASP3 5'UTR had a SNP (rs35372903, G/A) on binding site of miR-339-3p and this miRSNP and SNP (rs565188493, G/A) at miR-339-3p genomic sequence co-localized at the same genomic location of binding region. Therefore, this novel finding upon SNP cross-match between miR-339-3p and CASP3 5'UTR may give information about all these apoptotic processes. Consequently, this study revealed that computational approach to predict miRNA targets enables the course of narrowing down potential target sites for experimental validation and proves the significance of SNPs on target sites and miRNA geneomic sequences at target sites, especially 5'UTR and CDSs. We identified miRSNPs in the CASP3 gene and SNPs in miRNAs genes targeting 5'UTR and coding exons of CASP3.We assessed the impact of these miRSNPs and SNPs of miRNA genes with respect to apoptosis.We found 141 different miRNA binding sites and 6 different SNPs in binding sites, especially in 5'UTR.MiR-339-3p's binding site has a SNP on CASP3 5'UTR and its genomic sequence has a SNP at the same nucleotide.We report a strong association between miR-339-3p and apoptosis upon computational targeting analysis. Apoptosis is described as a mechanism of cell death occurring after adequate cellular harm. Deregulation of apoptosis occurs in many human conditions such as autoimmune disorders, ischemic damage, neurodegenerative diseases and different cancer types. Information relating miRNAs to cancer is increasing. miRNAs can affect development of cancer via many different pathways, including apoptosis. Polymorphisms in miRNA genes or miRNA target sites (miRSNPs) can change miRNA activity. Although polymorphisms in miRNA genes are very uncommon, SNPs in miRNA-binding sites of target genes are quite common. Many researches have revealed that SNPs in miRNA target sites improve or decrease the efficacy of the interaction between miRNAs and their target genes. Our aim was to specify miRSNPs on CASP3 gene (caspase-3) and SNPs in miRNA genes targeting 5'UTR and coding exons of CASP3, and evaluate the effect of these miRSNPs and SNPs of miRNA genes with respect to apoptosis. We detected 141 different miRNA binding sites (126 different miRNAs) and 7 different SNPs in binding sites of miRNA in 5'UTR and CDS of CASP3 gene. Intriguingly, miR-339-3p's binding site on CASP3 has a SNP (rs35372903, G/A) on CASP3 5'UTR and its genomic sequence has a SNP (rs565188493, G/A) at the same nucleotide with rs35372903. Also, miR-339-3p has two other SNPs (rs373011663, C/T rs72631820, A/G) of which the first is positioned at the binding site. Here, miRSNP (rs35372903) at CASP3 5'UTR and SNP (rs565188493) at miR-339-3p genomic sequence cross-matches at the same site of binding region. Besides, miR-339-3p targets many apoptosis related genes (ZNF346, TAOK2, PIM2, HIP1, BBC3, TNFRSF25, CLCF1, IHPK2, NOL3) although it had no apoptosis related interaction proven before. This means that miR-339-3p may also have a critical effect on apoptosis via different pathways other than caspase-3. Hence, we can deduce that this is the first study demonstrating a powerful association between miR-339-3p and apoptosis upon computational analysis.

Background: Inhibitor of growth (ING) tumor suppressor gene family has been discovered over the past decade and five different genes have been identified from ING1 to ING5. They have some functions like cell transcription regulation, cell cycle control, DNA repair and apoptosis. Because of the fact that ING3 gene expression has not been studied in breast cancer so far, we aimed to determine whether there was a relationship between ING3 gene expression and breast cancer prognostic factors. Methods: 46 female breast cancer patients in different stages were enrolled to our study. ING3 gene expressions obtained from tumoral and healthy breast tissue samples of patients were evaluated together with pathological and histological parameters. Results: The median age of the patients was 49 years. ING3 expression rate has been significantly higher in the tumor tissue compared to normal tissue and was statistically significant (p=0.001). In estrogen receptor (ER) and progesterone receptor (PR) positive patients, gene expression ratio was significantly higher than negative ones (p 0.05). Conclusions: This study was the first study on ING3 gene expression in breast cancer. ING3 gene expression has been shown to be associated with the receptor positivity and advanced stage disease. Further studies should be conducted on the prognostic significance of ING3 gene in breast cancer. Citation Format: Kalender ME, Cakir M, Ergun S, Oztuzcu S, Cengiz B, Ulasli M, Sevinc A, Camci C. Expression and role of ING3 gene in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-08.

Guney, Serkan/0000-0002-6270-5458; Petrovic, Nina/0000-0003-2503-1228 WOS: 000456869200006 PubMed: 30019650 Background: In recent years, targeted cancer treatment methods at various molecular levels have been developed for Non-Small Cell Lung Cancer (NSCLC), one of two major subtypes of lung cancer. miRNA-based clinical trials are currently the preferred targeted therapeutic strategy. Also, ceRNAs (competing endogenous RNA) would be the newest and the most effective approach to uncover novel interactions between mRNAs and miRNAs in NSCLC carcinogenesis. 'Mere are many factors influencing the efficiency of a miRNA to suppress or silence translation of the target mRNA. The most effective event is the presence of other RNAs showing ceRNA activity. These RNAs contain binding sites for specific miRNAs and enable miRNAs to bind these pseudo targets, instead of the original binding sites on the target mRNA. Therefore, the mRNA of the target gene is less affected by this miRNA, while the amount of miRNA remains the same in the media. Method: For this project, we determined that five clinically important different oncogenes (PDL1, FGFR1, DDX3X, SLC1A5, FXR1) are involved in the pathogenesis of NSCLC. For this purpose, we transfected model NSCLC cell line, A549, with miRNAs (miR-150-5p, miR-15a-5p, miR-503-5p) targeting these oncogenes to investigate whether these oncogenes will be suppressed at the mRNA level and also how the suppression efficiency of these miRNA on the oncogenes will be affected by possible ceRNA (CNKSR3, POU2F1, HIPK2) activities. Results: miR-15a-5p was determined to have the most suppressive effect on the five genes and three potential ceRNAs (p

MicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low- and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p = 0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p = 0.021 and p = 0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-204-5p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p = 0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.

Immune thrombocytopenic purpura (ITP) is a commonly acquired autoimmune bleeding disorder in children. MicroRNAs (miRNAs) are small RNAs which are found in cells and circulation, and play a role in protein synthesis and regulation. In this study, we aimed to determine a biomarker for childhood ITP comparing the plasma miRNA levels of children having ITP with healthy children. A total of 86 patients with ITP and 56 healthy children followed up by the Department of Pediatric Hematology and Oncology in University of Gaziantep since July 2011 were enrolled in the study. The 86 patients with ITP were evaluated in two groups as 43 acute ITP (aITP) and 43 chronic ITP (cITP) patients. Plasma expression levels of 379 miRNAs were investigated by RT-PCR (quantitative RT-PCR) technique and they were compared between aITP, cITP, and control groups. For all miRNAs, the average of raw quantification cycle values of three groups separately in the analysis chip was accepted as the reference gene value, and normalization was done according to this value. Statistically significant differences were detected in seven miRNAs (miR-302c-3p, miR-483-5p, miR-410, miR-544a, miR-302a-3p, miR-223-3p, and miR-597) investigated between the groups with respect to the expression levels. The expression rates were found to be over 95% in miR-302c-3p and miR-483-5p, over 75% in miR-410, and over 40% in miR-544, miR-302a-3p, and miR-223-3p in all three groups. The detection of significant differences between plasma miRNA levels of aITP and cITP patients and healthy children may provide useful information in the prediction of the course of disease, determination of disease etiopathogenesis, and the development of new therapeutic modalities.

Colorectal cancer (CRC) develops as a multi-step process which results from gradual accumulation of mutations in proto-oncogenes, tumor suppressor, and DNA repair genes. Mortality rate of CRC is very high. Therefore, development of alternative diagnostic methods which can be used in the early diagnosis is crucial. ATP2B4 gene encodes one of the four isoforms of p-type ATPase PMCA enzyme and bears critical importance in maintaining the balance of intracellular calcium homeostasis by providing the export of calcium ions out of the cell. ATP5B encodes a subunit of the mitochondrial ATP synthase which is an f-type ATPase. In this study, the relationship between ATP2B4 and ATP5B genes and CRC regarding gene expression was investigated. Study groups were constructed from a number of 50 patients (25 males, 25 females) with the mean age of 55.68 ± 9.4 and the gene expression levels in the healthy and cancerous tissues of the patients were compared by using semi-quantitative PCR and Real-Time PCR methods. As a result, in patients with rectum tumors, there was a significant relationship between ATP2B4 gene expression and the tumor location and in patients younger than 45 years, ATP5B gene expressions were detected significantly higher in tumor tissues by using RT-PCR. However, no significant relationship was detected in terms of expression differences of ATP2B4 and ATP5B genes between cancerous and healthy tissues of the CRC patients. ATP2B4 and ATP5B genes might have indirect associations in CRC pathogenesis and the investigation of their interactions with DNA repair and other related genes may help in understanding of CRC formation.

Familial mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder (MIM# 249100), particularly common in populations of Mediterranean extraction. MEFV gene, responsible for FMF, encoding pyrin has recently been mapped to chromosome 16p13.3. In the present study, 3,341 unrelated patients with the suspicion of FMF in south-east part of Turkey between the years 2009 and 2013 were enrolled and genomic sequences of exon 2 and exon 10 of the MEFV gene were scanned for mutations by direct sequencing. We identified 43 different type of mutations and 9 of them were novel. DNA was amplified by PCR and subjected to direct sequencing for the detection of MEFV gene mutations. Among the 3,341 patients, 1,598 (47.8 %) were males and 1,743 (52.1 %) were females. The mutations were heterozygous in 806 (62.3 %), compound heterozygous in 188 (14.5 %), homozygous in 281 (21.8 %) and mutations had complex genotype in 17 (1.32 %) patients. No mutation was detected in 2,051 (61.4 %) patients. The most frequent mutations were M694V, E148Q, M680I(G/C) and V726A. We could not find any significant differences between the two common mutations according to the gender. Molecular diagnosis of MEFV is a useful tool in clinical practice, thus a future study relating to genotype/phenotype correlation of FMF in more and larger group in Turkish population involving the whole MEFV gene mutations is necessary.

Background Urotensin-II (U-II) is a peptide recognized by its potent vasoconstrictor activity in many vascular events, however the role of urotensin-II in migraine has not been considered yet. The molecular mechanisms and genetics of migraine have not been fully clarified yet, but it is well-known that vascular changes considerably contribute in pathophysiology of migraine and also its complications. The aim of this study was to analyze the plasma U-II levels along with genotype distributions and allele frequencies for UTS2 Thr21Met and Ser89Asn polymorphisms among the patients with migraine without aura (MWoA). Methods One hundred eighty-six patients with MWoA and 171 healthy individuals were included in this study. Plasma U-II levels were measured in attack free period. The genotype and allele frequencies for the Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms in the UTS2 gene were analyzed. Results Plasma U-II levels were significantly higher in MWoA patients (p = 0.002). We detected a significant association between the T21M polymorphism in the UTS2 gene and migraine (53.8 % in patients, 40.4 % in controls, p = 0.035), but not with S89N polymorphism (p = 0.620). A significant relationship was found between U-II levels and MIDAS score (β = 0.508, p = 0.001). Conclusion Our study suggests that U-II may play a role in migraine pathogenesis; also Thr21Met polymorphism was associated with the risk of migraine disease. Further studies are needed for considering the role of U-II in migraine pathophysiology and for deciding if UTS2 gene may be a novel candidate gene in migraine cases.

Context: Dilated cardiomyopathy (DCM) is the most common cardiomyopathy in children. MicroRNAs (miRNA) are small RNAs which have regulatory functions in many biological processes.Objective: We aimed to determine miRNA expression levels in plasma of children with DCM.Materials and methods: Plasma expression levels of 379 miRNAs were compared between 23 DCM and 26 healthy children.Results: The expression levels of miR-618, miR-875-3p, miR-205, miR-194, miR-302a, miR-147, and miR-544 were found decreased. The expression levels of miR-518f and miR-454 were found increased in DCM patients.Discussion: miRNA level differences may provide the chance of using these miRNAs as new biomarkers.

It is known that high-dose radiation has an effect on tissue healing, but tissue healing does not occur when low dose radiation is applied. To clarify this issue, we compare the treatment success of low dose radiation with programmed cell death mechanisms on wounded tissue. In this study, we aimed to investigate the interactions of low and high-dose radiation using an autophagic mechanism. We included 35 adult Wistar-Albino rats in this study. All animals were injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tips of 18-gauge needles were used to develop a superficial scratching on the left cheek pouch mucosa by dragging in a linear movement on third and fifth days. After mucositis formation was clinically detected, animals were divided into five groups (n = 7). Different wavelengths of laser irradiations (1064 nm, Fidelis Plus, Fotona, Slovenia; 980 nm, FOX laser, A.R.C., Germany; 810 nm, Fotona XD, Fotona, Slovenia; 660 nm, HELBO, Medizintechnik GmbH, Wels, Austria) were performed on four groups once daily for 4 days. The laser irradiation was not performed on the control group. To get the tissue from the left cheek at the end of fourth day from all animals, oval excisional biopsy was performed. Molecular analysis assessments of pathological and normal tissue taken were performed. For this purpose, the expression analysis of autophagy genes was performed. The results were evaluated by normalization and statistics analysis. We found that Ulk1, Beclin1, and Atg5 expression levels were increased in the rats when the Nd:YAG laser was applied. This increase showed that a 1064-nm laser is needed to activate the autophagic mechanism. However, in the diode applications, we found that Beclin1, Atg10, Atg5, and Atg7 expressions numerically decreased. Atg5 is responsible for the elongation of autophagosome. Becn1 is a control gene in the control mechanism of autophagy. The reduction of the expression of these genes leads us to think that it may depend on the effect of drug (5-FU) used to form model. Expressions of therapeutic genes increase to ensure hemostasis, but in our study, expressions were found to decrease. More detailed studies are needed.

Competing endogenous RNAs (ceRNAs) are RNA transcripts which can communicate with each other by decreasing targeting concentration of micro-RNA (miRNA) with the derepression of other messenger RNAs (mRNAs) having the common miRNA response elements (MREs). Oncocers are ceRNAs taking crucial roles in oncogenic pathways processed in many types of cancer, and this study analyzes oncocer-mediated cross-talk by sponging microRNAs (miRNAs) in these pathways. While doing this, breast, liver, colon, prostate, gastric, lung, endometrium, thyroid and epithelial cancers and melanoma, rhabdomyosarcoma, glioblastoma, acute promyelocytic leukemia, retinoblastoma, and neuroblastoma were analyzed with respect to ceRNA-based carcinogenesis. This study defines, firstly, oncocers in the literature and contains all oncocer-related findings found up to now. Therefore, it will help to increase our comprehension about oncocer-mediated mechanisms. Via this study, a novel perspective would be produced to make clear cancer mechanisms and suggest novel approaches to regulate ceRNA networks via miRNA competition for cancer therapeutics. Graphical Abstract Multiple RNA transcripts have common MREs for the similar miRNA in their 3'-untranslated regions (3'-UTRs). Upregulation of ceRNAs rises the abundance of specific MREs and shifts the miRNA pool distribution, as a result, leading to the increased expression of target mRNA. The depot of genomic mutations and epigenetic alterations changing gene function and expression causes cancers. Herewith, genome-based somatic base-pair mutations, DNA copy number alterations, chromosomal translocation, also transcript fusions, alternative splicing are usually seen in cancer situations. Consequently, such cases causing changed UTR expression in transcripts influence the levels of MRE or present new MREs into the cells. Alterations in MREs of ceRNAs affect the capability of a specific mRNA transcript to attach or titrate miRNAs. As a result, the disturbed ceRNA network can lead to diseases and cancers. As a new term in RNA world, oncocers-the name for ceRNAs taking crucial roles in oncogenic pathways-are processed in many types of cancer, and oncocer-mediated cross-talk are analyzed by sponging miRNAs in these pathways.

HER2 (ErbB2/Neu) is a transmembrane tyrosine kinase belonging to the ERBB family of receptors. HER2/ErbB2 is also a well known proto-oncogene which is one of the most practiced molecules in the cancer area. A primary function of HER2 is suppressing apoptosis to enhance cell survival giving rise to uncontrolled proliferation and tumor growth. Caspases are well renowned proteases which are initiators as well as perfect finishers of the apoptotic process. The primary aim of this research was to study the expression levels of HER2 and apoptosis related factors CASP-3 and CASP-8 in several cancers including breast and other cancer cell lines and eventually to find a significant correlation between all these. Finally we obtained a result which clearly showed an increase in expression of HER2 in all cancer cell lines as compared to that of CASP-3 and CASP-8. As an addition to our present study, we also analyzed different natural miRNAs acting on ErbB2 and CASP3 using different miRNA databases. The bioinformatical analysis of the 3’-UTRs of ErbB2 revealed the target elements for miR-548d-3p and miR-559. It was also found that hsa-miR-375 is a common miRNA that binds to 3’-UTR region of both ErbB2 as well as to CASP-3 and in future we are in a plan to explore the role of these miRNAs in relation to ErbB2 and caspases. In summary we conclude that HER2 promotes cell survival by inhibiting apoptosis i.e. by downregulating CASP-3 and CASP-8. This research is a novel study and is expected to aid in better establishment of correlation between HER2 and caspases in different cancers.

The most common malignancy in women is breast cancer. Drug resistance in the treatment of cancer still remains a major clinical concern. Resistance to tamoxifen is seen in half of the recurrences in breast cancer. The antiestrogen tamoxifen gains agonistic property by transactivating ER alpha. PAK1-mediated phosphorylation of serine 305 (S305) of ER alpha leads to resistance to tamoxifen. In our study, PAK1-induced suggestive tamoxifen resistance was designed. According to our hypothesis, phosphorylation of ER alpha-S305 by PAK1 may be reversed by PAK1 transcriptional inhibition by miR-221-3p due to miR-221-3p targeting the 3' UTR of PAK1. For this purpose, we used Real-time PCR (qRT-PCR) to measure the expression level of miR-221-3p in ER-positive breast cancer cell lines (ZR-75-1, MCF7) and breast epithelial cell line, hTERT-HME1, as control in the laboratory incur department. The increase in the expression of PAK1 depending on miR-221-3p may be related to ZR-75-1 cell line which has invasive characteristic but other two ER+ cancer cell lines, MCF7 and HCC1500, have milder cancer severity. miR-221-3p may have a role on regulation of PAK1 expression because miR-221-3p expression level decreases while PAK1 expression level increases in SKBR3 cell line. miR-221-3p and PAK1 expressions in MDA-MB-231 cell line are higher than that of hTERT-HME1 cell line. This may mean that miR-221-3p has no regulatory effect on of PAK1 expression in this cell line. According to these results, miR-221-3p may give crucial information about molecular mechanism of the disease upon PAK1 activity or different mechanisms with respect to histopathology and severity of breast cancer. (C) 2014 Elsevier B.V. All rights reserved.

Background and objective: Hemophagocytic lymphohistiocytosis (HLH) is a life threatening hyper inflammatory disease. It is difficult to differentiate between primary and secondary HLH based on clinical findings at the onset of disease. We aimed to find parameters that can help to differentiate primary and secondary HLH at initial diagnosis especially for physicians working in developing countries.Patient and Method: We retrospectively analyzed data of 38 HLH patients who were admitted to the Pediatric Hematology Department of Gaziantep University between January 2009 and December 2013.Results: Of 38 patients, 20 were defined as primary and 18 were secondary HLH. The average age of primary and secondary HLH patients was 31±9 and 81±14 months, respectively (p=0.03). We found consanguinity rates significantly higher in primary HLH patients compared to secondary HLH patients (p=0.03). We found that total and direct bilirubin levels significantly increased in primary HLH patients compared to secondary HLH patients (p=0.006, p=0.044). Also, CRP levels were found markedly increased in secondary HLH patients compared to primary ones (p=0.017).Conclusion: We showed that cholestasis and hyperbilurubinemia findings of HLH patients at the initial diagnosis should be considered in favor of primary HLH and increased level of CRP should be considered in favor of secondary HLH.

Sagliker syndrome (SS) develops particularly before puberty while chronic kidney disease (CKD) reaches stage 3 with overt secondary hyperparathyroidism. We conducted screening for mutations in all the 13 exons of GNAS1 gene, all 3 exons of FGF23, and all 18 exons in FGFR3 genes in 23 patients. In 73.9% (17 of 23) patients, 17 genetic abnormalities in GNAS1 were detected. Seven (58.3%) of 12 nucleotide alterations comprised novel missense mutations and 3 nonsense. Mismutations were in different manner. There were also 6 heterozygous transversion polymorphisms in exons. Six were introngenic mutations (introns 65626, 70387, 70817). We found 10 mutations with different manner in FGF23 gene. Two were defined previously but remaining 8 were novel mutations. Three were in intronic region near exon 2. We sequenced all exons and intronic regions near exon-exon junction regions of FGFR3 gene. We found 22 mutations with different manner. Six were defined previously and remaining 16 were novel mutations. Eight of them were in intronic region near exon 11 and the last 2 were in noncoding exonic region of exons. One was in the exon-exon junction region between exon 11 and 12, therefore this mutation might be preventing splicing of this intron. Because the incidence of CKD late stage 3 is around 8% but the incidence of SS is around 0.5% in CKD, these gene mismutations might be responsible for bone deformities such as McCune-Albright syndrome and achondroplasias. Although our patients were not resembling any of them, they could be in between, and SS might be a combination-compulsion of bone dysplasias-hereditary osteodystrophies and CKD.

Caspases are a family of proteases that function as the primary mediators of apoptosis. miR-221 is an oncogenic miRNA that may have both anti-angiogenic and angiogenic effect. The aim of this work was to compare the expression levels of miR-221 and its target caspase-3 in different cancer cell lines and to find out a relationship between these two. We also analyzed binding efficiency of miR-221 to 3’UTR region of CASP3 gene computationally. Our results indicate that expression of caspase-3 is quite lower as compared to miR-221 expression in all of the selected cancer cell lines. Also, our computational results showed that miR-221-3p, of which binding site has two SNPs (rs369703524, C/T; rs189187745, T/A) on CASP3 3’UTR region. As a result, we conclude that miR-221 may have a crucial role in repressing the expression of caspase-3 which may contribute to a lower apoptotic rate, thus supporting the selection of more aggressive cancer cells.

MicroRNAs can regulate many biological functions. miR-122-5p has a tumor suppressor function through different molecular pathways. Also, our second hit, ADAM10, targeted by miR-122-5p, is a major determinant of HER2 shedding causing that trastuzumab cannot bind to HER2 receptors. Therefore, our analysis upon ADAM10 expression and miR-122-5p was a good point to understand molecular mechanism of breast cancer. In our study, we investigated the expression profiles of miR-122-5p and its target ADAM10 in 71 breast cancer patients. Immunohistochemical analysis of ER, PR and HER2 gene products was used to categorize tumors in patients. Expression data and immunohistochemical findings were evaluated to comment on the relationship between miR-122-5p and ADAM10. ADAM10 expression was higher in tumor than that of normal tissue but miR-122-5p expression was lower in tumor than that of normal tissue. The expression pattern in HER2+ patients was reverse of the overall result. It can be explained like that miR-122-5p expression increases especially in HER2+ cancer cell to suppress ADAM10 shedding activity on HER2 receptor. However, increase in expression of tumor suppressor miR-122-5p is not enough to inhibit ADAM10. All in all, we can think miR-122-5p as potential regulator of ADAM10 and trastuzumab resistance. Since if we increase miR-122-5p activity together with trastuzumab administration, then HER2+ breast cancer cells may overcome trastuzumab resistance by inhibiting ADAM10 shedding activity on HER2 receptors and increase the efficiency of trastuzumab.

Apoptotic signaling pathways. Three main caspases-dependent apoptotic signaling pathways were schematized here. (a) Cytokines/Fas-mediated extrinsic pathway: the Fas receptor binds the Fas ligand (FasL), a transmembrane protein part of the TNF family. The interaction between Fas and FasL results in the formation of the death-inducing signaling complex (DISC), which contains the FADD, caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates caspase-3, and triggers the execution of apoptosis of the cell. In other types of cells (type II), the Fas-FADD starts a feedback loop that spirals into increasing release of proapoptotic factors from mitochondria and the amplified activation of caspase-8. (b) Mitochondrial-mediated intrinsic pathway: permeabilisation of the mitochondria and release of cytochrome c into the cytoplasm are realized. Cytochrome c then forms a multi-protein complex known as the 'apoptosome' and initiates activation of the caspase cascade through caspase-9. (c) Endoplasmik reticulum (ER)/Ca-mediated pathway: caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals.SNPs in the miR-4802-3p and in the binding site with 3'UTR of CASP3. MiR-4802-3p's binding site has a SNP (rs386513603, T/C) in the CASP3 3'UTR and its genomic sequence has a SNP (rs372435266, A/T) at the same nucleotide with rs386513603 and another SNP (rs190144655, C/T) at another site of the binding region. MiRSNP (rs386513603) at the CASP3 3'UTR and SNP (rs372435266) at miR-4802-3p genomic sequence cross-matches at the same site of binding region.Display Omitted We identified miRSNPs in the CASP3 gene and SNPs in miRNAs genes targeting 3'UTR of CASP3.We assessed the impact of these miRSNPs and SNPs of miRNA genes with respect to apoptosis. We found 89 different miRNA binding sites for 43 different miRNAs and 16 different SNPs in binding sites.MiR-4802-3p's binding site has a SNP on CASP3 3'UTR and its genomic sequence has a SNP at the same nucleotide.We report a strong association between miR-4802-3p and apoptosis upon computational targetting analysis. Apoptosis is a strictly organized course which keeps the healthy survival/death equilibrium. Disregulation in apoptosis may lead autoimmunity or cancer, but increased apoptosis can lead degenerative diseases. Studies during the last several years have identified numerous affected miRNAs in association with apoptosis, their target genes and biological functions, and possible drug interventions. Polymorphisms in miRNA genes or miRNA target sites (miRSNPs) can modify miRNA action. While polymorphisms in miRNA genes are relatively rare, SNPs in miRNA-binding sites in target genes are more frequent. Several studies have shown that SNPs in miRNA target sites enhance or weaken the interaction between miRNA and its target transcripts and are associated with cancers and other diseases. We aimed to identify miRSNPs on executioner caspase, CASP3 gene (caspase-3) and SNPs in miRNA genes targeting 3'UTR of CASP3 and assessing the impact of these miRSNPs and SNPs of miRNA genes targeting 3'UTR of CASP3 with respect to apoptosis. We identified 89 different miRNA binding sites (for 43 different miRNAs) and 16 different SNPs in binding sites of miRNA in the 3'UTR of the CASP3 gene. Also, 2 SNPs (rs372435266 and rs190144655) were found on this miRNA' genomic sequence. One of them crossmatched with a SNP in the 3'UTR of CASP3 that we found formerly. This miRNA was miR-4802-3p. Besides, miR-4802-3p targets three other apoptosis related genes, XIAP, IL1A and SOX2. This means that miR-4802-3p may also have a critical effect on apoptosis via different pathways other than caspase-3. We can therefore conclude that this is the first study proving a strong association between miR-4802-3p and apoptosis upon computational targetting analysis.

Caspases are important initiators and most well-known finishers of apoptosis. By changing the death propagation homeostatic equilibrium, their different expression patterns might trigger the progression of hazardous diseases like cancer. miR-221 is an oncogenic miRNA. It is known to have both anti-angiogenic and angiogenic effect. The aim of this work was to compare the expression levels of miR-221 and its target caspase-3 in different cancer cell lines and to find out a relationship between these two. We also tried to establish a prominent relationship between miR-221 and its role in apoptosis by studying their expression levels. Our results indicate that expression of caspase-3 is quite lower as compared to miR-221 expression in all of the selected cancer cell lines. As a result, we conclude that miR-221 may have a crucial role in repressing the expression of caspase-3 which may contribute to a lower apoptotic rate, thus supporting the selection of more aggressive cancer cells. To our knowledge, this is the first study related to the expression levels of caspase-3 and miR-221 in different cell lines at the same time. We expect that our study might pave the way for better understanding the role of miR-221 in apoptotic regulation of caspase-3.

Beta (β)-thalassemia is the most frequently observed hereditary blood disorder in the world. It is characterized by deficiency of hemoglobin β-globin gene and is also a profoundly heterogeneous both at the molecular and clinical level. In the case of β-thalassemia, there is reduced (β+ type) or absent (βo type) synthesis of the beta chains of hemoglobin. β-Thalassemia clinically occurs in three main forms: major, intermedia and minor according to requirement of transfusion. The objective of this study was to evaluate β-thalassemia mutations in 89 patients ranging from 2 months to 16 years of age, who enrolled to Medical School Research and Training Hospital, Gaziantep University. The direct DNA sequence analysis was performed for mutation scanning of β-globin gene. 89 children with β-Thalassemia including all types were analyzed, 16 different β-thalassemia mutations were detected. We have also identified a novel mutation (HBB.c.-80delT, rs397509430) in the promoter region (−30 TATA box) of β-globin gene, and clinical data of patient having novel mutation was given. The β-Thalassemia mutations were determined as β-Thalassemia major type in 42 patients (47.19 %), β-Thalassemia intermedia in 4 (4.49 %), β-Thalassemia minor in 43, (48.31 %) patients. The most frequent mutation was IVS I-110 G>A, followed by IVS I-1 G>A, IVS I-6 T>C, IVS II-1 G>A, respectively.

HER2/ErbB2, a known proto-oncogene (also known as HER2, neu), is among the most practiced molecules in the cancer area. Human epidermal growth factor receptor 2 (HER2) is over expressed in approximately 20-30 % of breast cancer tumors and also in a lot of other human cancer types. It is known to be related to the aggressiveness of the disease, increased mortality and higher relapse ratio. The unusual HER2 overexpression is associated with more severe disease characteristics in several cancers. In recent past, there have been remarkable advances in understanding the role of the HER2 gene in cancers. Caspases are well renowned proteases that act as essential initiators and executioners of the apoptotic process. The primary function of HER2 is suppressing apoptosis to enhance cell survival and eventually giving rise to uncontrolled proliferation and tumor growth. The objective of this work was to study the expression levels of HER2 and apoptosis related factors CASP-3 and CASP-8 in several breast and other cancer cell lines and finally to find a meaningful correlation between all these. We summed up by obtaining an increase in expression of HER2 in all cancer cell lines as compared to that of CASP-3 and CASP-8. In summary we conclude that HER2 promotes cell survival by inhibiting apoptosis i.e. by downregulating CASP-3 and CASP-8. This is a novel study comprising the expression study of HER2 and different caspases in different cancer cell lines simultaneously. It is thus expected that this study will aid in better establishment of correlation between HER2 and caspases in different malignancies.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life threatening hyper inflammatory disease. Micro RNAs (miRNA) are about 22 nucleotide-long, small RNAs encoded with genes, and they have regulatory functions in immune response. Objective: To determine the miRNA expression levels of 11 secondary HLH patients, we evaluated the associations of miRNA levels with pathogenesis, clinical presentation, and prognosis of the disease. Patients and Methods: Patients who were diagnosed with secondary HLH from January 2011 to December 2012 were included in this study. We profiled the expressions of 379 miRNAs in plasma of both HLH patients and healthy controls. Patients were evaluated regarding with age, clinical findings, miRNA expresions, laboratory data, treatment, and prognosis, by using descriptive statistics. Results: A total of 11 secondary HLH patients and 11 healthy children were included in this study. miR-205-5p was expressed in all case and controls and expression level of miR-205-5p was found 6.21 fold higher than control group (p=0.01). We detected the second highest expression percent in miR-194-5p with 81% of cases and controls. Expression level of miR-194-5p was found to have 163 fold higher than controls (p= 0.009). miR-30c-5p showed 77% expression percent in cases and controls together. The expression level of this miRNA was detected 9 fold decreased in HLH patients compared to healthy children (p= 0.031). Conclusion: We showed that miR-205-5p, miR-194-5p and miR-30c-5p could be useful plasma biomarkers for HLH. Further research is needed in larger and homogenous study groups, especially for these miRNAs as biomarkers for HLH.

We report a case of a 3-month-old Turkish girl who had clinical and laboratory features of Glanzmann's thrombasthenia associated with asymmetric crying facies (ACF). Although ACF is a minor anomaly, it should not be forgotten that it can be accompanied by major congenital anomalies and if this finding is detected, other anomalies should be investigated.

Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in south-east part of Turkey between the years 2010 and 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1 −675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57, 0.25, 2.61, 13.78, 9.34 and 24.27 % in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43, 3.44, 24.91, 44.94, 41.09 and 45.66 %, respectively. No mutation was detected in 92 (1.95 %) patients in total. Because of the fact that this is the first study to screen six common mutations in CVD panel in south-east region of Turkey, it has a considerable value on the diagnosis and treatment of these diseases. Upon the results of the present and previous studied a careful examination for these genetic variants should be carried out in thrombophilia screening programs, particularly in Turkish population.