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Herein, we identified miRNA signatures that were able to differentiate malignant prostate cancer from benign prostate hyperplasia and revealed the therapeutic potential of these miRNAs against prostate cancer development. MicroRNA expressions were determined by qPCR. MTT was used for cell viability analysis and immunohistochemistry was performed for Bax/Bcl-2 staining. ELISA was used to measure MMP2/9 levels. Wound healing assay was used for the evaluation of cell migration. Notably, expression levels of miR-125b-5p, miR-145-5p and miR-221-3p were significantly reduced in prostate cancer patients as compared to BPH patients. Moreover, ectopic expression of miR-125b-5p, miR-145-5p and miR-221-3p resulted in significant inhibition of cell proliferation and altered cell morphology. Also, expression level of Bax protein was increased while Bcl-2 level was reduced in cells treated with miR-125b-5p, miR-145-5p and miR-221-3p mimics. Enhanced expression of miR-125b-5p, miR-145-5p and miR-221-3p was also significantly altered the expression of caspase 3 and 8 levels. In addition, MMP9 levels were significantly reduced in cells ectopically expressing miR-221-3p. All miRNA mimics significantly interfered with the migration of prostate cancer cells. Consequently, our findings point to an important role of these three miRNAs in prostate cancer and indicate that miR-125b-5p, miR-145-5p and miR-221-3p are potential therapeutic targets against prostate cancer.

Long noncoding RNAs (lncRNAs) constitute the largest class of noncoding RNAs and play significant roles in the development of cardiovascular pathologies. In the present study, we aimed to evaluate whether 4 candidate lncRNAs – MIAT, MEG3, MALAT1, and MCM3AP-AS1 – have distinct expression levels in patients with obstructive coronary artery disease (CAD) and reveal the diagnostic and therapeutic potentials of these lncRNAs for CAD. A total of 90 patients who subjected to coronary angiography were enrolled. Relative expression of lncRNAs were assayed using qRT-PCR methodology. As a result, MIAT was downregulated, while MEG3 was upregulated in CAD patients. Receiver operating characteristic curves demonstrated that these lncRNAs have a high potential to provide sensitive and specific diagnosis of CAD. The calculated area under curve levels indicated that MIAT and MEG3 have high diagnostic value for detecting the presence of significant CAD. However, MALAT1 and MCM3AP-AS1 levels were not sufficiently reliable for CAD development in our cases. Here, we demonstrate that MIAT and MEG3 were differentially expressed in our patients and might be promising biomarkers and therapeutic targets for CAD. These results indicate that MIAT and MEG3 could play chief roles in CAD development.

Illuminating the correlations between non-coding RNAs and protein-coding genes are of great interest to understand more about the molecular mechanisms that drive malignant transformation and understanding such correlations will enable development of more specific and efficient targeted therapeutics. Accordingly, in this comprehensive meta-analysis study, we tried to determine correlations between long non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) molecules that are involved in the pathogenesis of colorectal cancer (CRC). For the present study, current colorectal cancer studies published until 20 August 2017 and associated with the lncRNA-miRNA-mRNA interactions was included. The current literature search was done online in Pubmed, Embase and Web of Science databases. These databases have been screened with three keywords; “lncRNA”, “miRNA” and “colorectal cancer”. As a result, colorectal neoplasia differentially expressed (CRNDE) was determined to be consistently up-regulated in CRC tissues and inversely associated with miR-181a-5p. Also, CRNDE expression was significantly associated with lymph node metastasis (p = 0.032). Additionally, a significant association was determined between CRC and survival time in the OS analysis of FER1L4, TUSC7, UCC and lincRNA-ROR. More importantly, there was a negative correlation between lncRNA-miRNA expressions (p = 0.001). Particularly, CRNDE/miR-181a-5p, FER1L4/miR-106a-5p, TUSC7/miR-211, UCC/miR-143 and lincRNA-ROR/miR-145 was negatively correlated. In addition, there was a significant positive correlation between GAPLINC/CD44 and TUSC7/CDK6 in CRC tissues (p = 0.000). Overall analysis showed that lncRNAs and mRNAs, which are targets of the same miRNA, have positive interactions. In addition, miRNAs were shown to have negative correlations with target lncRNA/mRNA.

Background Micro RNAs (miRNAs) are key regulators of gene expression and play important roles in the pathogenesis of cardiovascular diseases. We aimed to test whether five novel candidate miRNAs have different expressions in patients with obstructive coronary artery disease (CAD) and acute ST-segment elevation myocardial infarction (STEMI). Methods In this study, total 135 patients with angina or acute myocardial infarction who underwent coronary angiography were recruited and divided into 3 groups: 45 patients with normal coronary arteries, 45 patients with obstructive CAD and 45 patients with acute STEMI. Serum which was obtained from blood samples were drawn before coronary angiography. After RNA isolation and cDNA synthesis, expressions of miRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis of qRT-PCR expression results was carried out by using the 2−ΔCt formula. Results Expression differences were statistically significant for the four studied candidate miRNAs (hsa-miR-128-3p, hsa-miR-196a-5p, hsa-miR-373-3p and hsa-miR-375) among the groups. The receiver operating characteristic curves indicated that three studied candidate miRNAs (miR-196a-5p, miR-373-3p and miR-375) had high potential to provide sensitive and specific diagnostic value for Acute Coronary Syndrome (ACS). The calculated Area under curve (AUC) levels showed that miR-196a-5p (AUC: 0.64; 95% CI: 0.521–0.759; p = 0.032) for obstructive CAD and STEMI groups, miR-373-3p (AUC: 708; 95% CI: 0.605–0.812; p Conclusion We demonstrated that miR-196a-5p, miR-373-3p and miR-375 are expressed differently in our patients and that these miRNAs may become a promising biomarker for these diseases since they have diagnostic value for CAD and ACS.

The transcribed ultra-conserved regions (T-UCRs) are a novel family of non-coding RNAs which are absolutely conserved (100%) across orthologous regions of the human, mouse, and rat genomes. T-UCRs represent a small portion of the human genome that is likely to be functional but does not code for proteins and is referred to as the "dark matter" of the human genome. Although T-UCRs are ubiquitously expressed, tissue- and disease-specific expression of T-UCRs have also been observed. Accumulating evidence suggests that T-UCRs are differentially expressed and involved in the malignant transformation of human tumors through various genetic and epigenetic regulatory mechanisms. Therefore, T-UCRs are novel candidate predisposing biomarkers for cancer development. T-UCRs have shown to drive malignant transformation of human cancers through regulating non-coding RNAs and/or protein coding genes. However, the functions and fate of most T-UCRs remain mysterious. Here, we review and highlight the current knowledge on these ultra-conserved elements in the formation and progression of human cancers.

Prostate cancer is a widespread global malignancy and responsible for the significant number of deaths. TMPRSS2-ERG fusion, which arises in approximately 50% of prostate cancer, leads to overexpression of the ERG gene and advances migration and invasion capacity of prostate cancer cells. In prostate cancer with TMPRSS2-ERG fusion, determination of miRNA expression profile and elucidation of the underlying mechanism is important. Accordingly, here we aimed to decipher miRNAs that are related with the TMPRSS2-ERG fusion in prostate cancer using TCGA prostate cancer findings. Firstly, TCGA prostate cancer data sets were obtained and samples with unknown ERG fusion status and clinical data were excluded from the study. Patients with available mRNA and miRNA expression data were included in the study. As a result, in patients with TMPRSS2-ERG fusions, mRNA levels of PLAT, NDRG1 and SPINT1 were shown to be elevated whereas expression levels of CXCR4 and HPGD genes were shown to be reduced. In addition, there was a significant negative correlation between TMPRSS2-ERG fusion and miR-221, miR-196a, and a significant positive correlation between TMPRSS2-ERG fusion and miR-200c and miR-196b. Also, there was a significant negative correlation between HPGD and miR-21, and MYC and miR-145, whereas there was a significant positive correlation between CXCR4 and miR-199a, and HPGD and miR-146b. Consequently, findings of the present study strongly indicated that TMPRSS2-ERG fusion alters miRNA expression profile in prostate cancer and miRNAs associated with the TMPRSS2-ERG fusion can be interesting candidates for future targeted prostate cancer therapies.

Loss of tumor suppressor activity is a frequent event in the formation and progression of tumors and has been listed as an important hallmark of cancers. Microtubule-Associated Scaffold Protein 1 (MTUS1) is a candidate tumor suppressor gene which is reported to be frequently down-regulated in a variety of human cancers including pancreas, colon, bladder, head-and-neck, ovarian, breast cancers, gastric, lung cancers. It is also reported to be implicated in several types of pathologies such as cardiac hypertrophy, atherosclerosis, and SLE-like lymphoproliferative diseases. Moreover, MTUS1-encoded proteins are shown to be involved in the regulation of vital cellular processes such as proliferation, differentiation, DNA repair, inflammation, vascular remodeling and senescence. However, the current knowledge is very limited about the role of this gene in human cancers as well as other type diseases. Besides, there is no literature report which summarizes and criticizes the importance of MTUS1 in the cellular processes, especially in the processes of carcinogenesis. Accordingly, in this comprehensive review, we tried to shed light on the role of tumor suppressor MTUS1/ATIP in health and disease, putting special emphasis on its role in the development and progression of human cancers as well as associated molecular mechanisms and the reasons behind MTUS1/ATIP deficiency, which have been not well documented previously.

Objectives: The aim of the present study was to demonstrate the key role of differential expression levels of RB1, TP53, XIAP, BCL2 AIFM3, BAX, CASP3 and CASP9 genes in odontogenic cysts. Materials and Methods: A total number of 15 patients who diagnosed with odontogenic cyst were enrolled for the present study. For the quantitative gene expression analysis, cyst and adjacent gingival healthy tissues of patients were collected during surgical assessments. Quantitative analysis of gene expression levels RB1, TP53, XIAP, BCL2 AIFM3, BAX, CASP3 and CASP9 were achieved real-time PCR method. For the optimization of gene expression levels GAPDH reference gene was used. Results: Expression of both RB1 and TP53 genes were markedly diminished in odontogenic cysts tissues as compared to healthy tissues (p0.05). Conclusions: The findings of the present study indicates that RB1, TP53, XIAP, CASP3 and CASP9 genes might have chief roles in formation odontogenic cysts and responsible for the increased cell proliferation in these tissues.

Multiple sclerosis (MS) is an imflammatory disease of central nervous system caused by genetic and environmental factors that remain largely unknown. Autophagy is the process of degradation and recycling of damaged cytoplasmic organelles, macromolecular aggregates, and long-lived proteins. Malfunction of autophagy contributes to the pathogenesis of neurological diseases, and autophagy genes may modulate the T cell survival. We aimed to examine the expression levels of autophagy-related genes. The blood samples of 95 unrelated patients (aged 17-65years, 37 male, 58 female) diagnosed as MS and 95 healthy controls were used to extract the RNA samples. After conversion to single stranded cDNA using polyT priming: the targeted genes were pre-amplified, and 96×78 (samples×primers) qRT-PCR reactions were performed for each primer pair on each sample on a 96.96 array of Fluidigm BioMark™. Compared to age- and sex-matched controls, gene expression levels of ATG16L2, ATG9A, BCL2, FAS, GAA, HGS, PIK3R1, RAB24, RGS19, ULK1, FOXO1, HTT were significantly altered (false discovery rate

Mammalian Sirtuins have been shown to perform distinct cellular functions and deregulated expression of these genes was reported to be involved in the development of various malignancies including breast cancer. An increasing number of evidence indicates that Sirtuins have both tumor promoter and tumor suppressor functions. However, the roles of Sirtuins have not been well-reported in breast cancer. In the present study, quantitative expression levels of Sirtuins (SIRT1-7) in breast cancer patients and breast cancer cell lines (MCF-7 and SKBR3) and control cell line (CRL-4010) were assessed by using a high-throughput real-time PCR method. As a result, Sirtuins were found to be differentially expressed in breast cancer tissues and cancer cell lines. Particularly, expressions of SIRT1 and SIRT4 were found to be significantly down-regulated in breast cancer tissues and SKBR3 breast cancer cells. In contrast, SIRT2, SIRT3, and SIRT5 genes were shown to be up-regulated in our study. Although SIRT6 and SIRT7 were also up-regulated in breast cancer tissues, these expression changes were statistically insignificant. Additionally, SIRT2, SIRT3, SIRT5, SIRT6 and SIRT7 were found to be differentially expressed in breast cancer cell lines. Yet, these changes were not well-correlated with tissue expression levels. In conclusion, Sirtuin family of genes shows differential expressions in breast cancer tissues and cells and SIRT1 and SIRT4 seem to play key tumor suppressor roles in breast cancer development. Herein, we report expression levels of Sirtuin family of genes in both breast cancer tissues and cancer cell lines simultaneously.

Osteosarcoma is a most frequent primary solid malignant disease of bone, mainly affecting children and adolescents. Although several factors are involved in osteosarcoma development, genetic factors seem to play a chief role in the induction and advancement of osteosarcoma. AKT1 is an oncogenic protein that is highly deregulated in a variety of human malignancies including osteosarcoma. By the discovery of small RNA molecules called miRNAs, our understanding of post-transcriptional regulation of molecular mechanisms is considerably evolved. Also, the role of miR-125b-5p in osteosarcoma still muchly remains controversial. Specifically, miR-125b-5p- AKT serine/threonine kinase 1 (AKT1) axis has not been previously reported in osteosarcoma. Accordingly, in this particular study, for the first time, we reveal the miR-125b-5p-mediated regulation of AKT1 in osteosarcoma development. U2-OS osteosarcoma cells were used as an osteosarcoma cell line model. To ectopically overexpress miR-125b-5p in U2-OS osteosarcoma cells, synthetic miRNA mimics targeting miR-125b-5p were used. Quantitative RT-PCR method was used for the analysis of gene expressions. Significant overexpression of miR-125b-5p was observed following 72 h of mimic transfections (p

Osteosarcoma is the most common primary malignancy arising from bone. Increasing mass of indications suggest that long non-coding RNAs (lncRNAs) play crucial roles in the development of progressions of human cancers including osteosarcoma. Although several lncRNAs have shown to be involved in the molecular pathogenesis of osteosarcoma, identification of novel lncRNAs involved in the osteosarcoma pathobiology remained muchly elusive. Besides, ARID3A is a member of ARID family of DNA binding proteins. ARID3A was also implicated in osteosarcoma pathogenesis. Accordingly, in the present study, we mechanistically investigated the effect of ARID3A on the expression of TP73 and TP73-AS1 in osteosarcoma cells and to determine the relationship between them. For the overexpression of ARID3A in U2-OS cells, pER_xpress_ARID3A expression vector and for the silencing of ARID3A, ARID3A-spesific siRNA was used. Expression levels of ARID3A, TP73 and TP73-AS1 genes were determined by qPCR method. As a result, expression levels of TP73-AS1 were well-correlated with the ARID3A expression levels whereas TP73 expression levels were not well-correlated with ARID3A. In conclusion, our results indicate that ARID3A might be involved in the regulation of TP73-AS1 in osteosarcoma. To our knowledge, this is the first study revealing the role of ARID3A in the regulation of TP73 and TP73-AS1 genes.

Long non-coding RNAs have recently appeared as fundamental regulators of gene transcription in several biological processes, but only a few have known functional influences in the malignant transformation of breast cancer. CDKN2B-AS1 gene, also termed ANRIL, encoding a long non-coding RNA is located in the CDKN2B-CDKN2A gene cluster, loss of which is the most frequent alternation in several types of human malignancies. CDKN2B-AS1 is involved in the suppression of tumor suppressor genes (INK4a, ARF, and INK4b) and has been recognized as a direct target of E2F1. However, the roles of E2F1–CDKN2B-AS1 interaction in breast cancer have remained muchly mysterious. In this particular study, we reveal that both CDKN2B and CDKN2B-AS1 genes were differentially expressed in breast cancer cells in contrast to breast epithelial cells. Ectopic expression of E2F1 activated CDKN2B-AS1 but not CDKN2B expression. Lastly, overexpression of E2F1 improved the colony formation and migratory capacities of breast cancer cells. These results suggest that enhanced E2F1 activity increased invasive and proliferative activity of breast cancer but not breast epithelial cells possibly through up-regulating CDKN2B-AS1 transcript.

Aim: In colorectal cancer (CRC), expression of genes involved in the PI3K/Akt signaling pathway varies significantly. Studies haveshown that microRNAs (miRNA) have important roles in the development of CRC. Accordingly, the aim of this study was to determinemiRNAs affecting the critical genes in the PI3K/Akt pathway by analysis of The Cancer Genome Atlas (TCGA) CRC data sets and toevaluate the clinical significance of these miRNAs.Material and Methods: Initially, CRC mRNA, miRNA expression levels and patient data were obtained from TCGA database. The studyincluded 220 CRC patients. MiRNAs that were negatively correlated with genes in the PI3K/Akt signaling pathway were selected, andtheir expression levels were compared with the clinical and demographic characteristics of CRC patients.Results: miR-18a, miR-19b, miR-17, miR-106b, miR-130b and miR-135b were found to be negatively correlated with genes that playkey roles in the PI3K/Akt pathway. Also, miR-18a, miR-19b, miR-17 and miR-135b were found to vary significantly according to theCRC subtype.Conclusion: Consequently, the PI3K/Akt signaling pathway was found to be deregulated in CRC and the majority of genes involved inthis signaling pathway were associated with miRNAs. Thus, PI3K/Akt miRNA axis might serve as a potentially distinctive diagnostic,prognostic and therapeutic avenue against CRC.

Deregulated microRNA (miRNA) expression has been shown to be involved in the pathogenesis of several types of cancers including colorectal cancer (CRC). Thus, determining miRNA targets of genes that play critical role in the malignant transformation is very important. Here, expression levels of tumor suppressor microtubule-associated tumor suppressor 1 (MTUS1) and its regulatory miRNAs were reported. Predicted and validated targets of MTUS1 gene was determined by a computational approach. Expressions of MTUS1 and miRNAs were determined by using 96.96 Dynamic Array™ integrated fluidic circuit (Fluidigm). As a result, MTUS1 levels were found to be diminished in formalin-fixed, paraffin-embedded (FFPE) tissue samples of CRC patients compared to controls. Also, several of MTUS1 targeting miRNAs were found to be upregulated in CRC samples (miR-373-3p, 183-5p, 142-5p, 200c-3p, 19a-3p, -20a-5p, -181a-5p, -184, -181d-5p, -372-3p, 27b-3p, 98-5p, -let-7i-5p, -let-7d-5p, -let-7g-5p, -let-7b-5p, and -let-7c-5p). Of these miRNAs, miR-135b-5p, -373-3p, 183-5p, 142-5p, 200c-3p, 19a-3p showed marked expression levels. In contrast, expression levels of let-7a-5p, 7e-5p, 7f-5p, hsa-miR-125a-5p, and 125b-5p were found to be downregulated in CRC tissues. Accordingly, some of the overexpressed miRNAs especially the miR-135b-5p, -373-3p, 183-5p, 142-5p, 200c-3p, and 19a-3p may play key roles in CRC pathophysiology through MTUS1. In contrast, let-7a-5p, 7e-5p, 7f-5p, miR-125a-5p, and 125b-5p may play important roles in CRC carcinogenesis independent from the MTUS1. In conclusion, MTUS1 targeting miRNAs may play key roles in the development of CRC by downregulating tumor suppressor MTUS1.

Breast cancer is the most common malignancy predominantly affecting women. To date, numerous numbers of studies were reported novel genetic contributors with diagnostic, prognostic, and therapeutic potential for the breast carcinogenesis. However, the role of urotensin-II in breast carcinogenesis has not been elucidated yet. Urotensin-II is a somatostatin-like cyclic tiny peptide identified by its potent vasoconstrictor activity. Soon after its discovery, its involvement in many disease states as well as its expression in various tissues including the tumors have been demonstrated. Moreover, there is strong evidence that suggest urotensin-II as the significant contributor of angiogenesis as well as cell proliferation and tumor biology. In this study, enzyme-linked immunosorbent assay (ELISA) and restriction fragment length polymorphism analysis were used to evaluate plasma levels of urotensin-II and Thr21Met and Ser89Asn polymorphisms of UTS2 gene in breast cancer patients. In the present case-control study, we noticed a significant decrease in the levels of urotensin-II protein in the plasma of the breast cancer patients (p 0.05). Also, Thr21Met polymorphism in the UTS2 gene was associated with the risk of developing breast cancer (p 0.0001), whereas the genotype frequency of Ser89Asn was found to be similar in patients and controls (p 0.05). In addition, we demonstrated the gradual decreasing of urotensin-II protein levels from TT and TM to MM genotypes. In conclusion, these results strongly suggest that urotensin-II could contribute to breast carcinogenesis and Thr21Met polymorphism can be an important risk factor in developing breast tumors.

Thyroid cancer is the most common type of endocrine malignancy and a leading cause of death among endocrine organ-related cancers. Similar to other types of cancers, early diagnosis of thyroid cancer is important to increase the survival and treatment of this disease. Several immunohistochemical markers are used in the differential diagnosis of thyroid papillary carcinoma. Also, increasing evidence indicates that P-element induced wimpy testis like 2 (PIWIL2) is an RNA-binding protein involved in the induction and progression of numerous types of human malignancies such as lung, breast, colon, prostate and cervix cancers. However, the role of PIWIL2 was poorly investigated in thyroid cancers. Accordingly, aim of the present study was to elucidate the relationship between PIWIL2 and thyroid cancers. The expression level of PIWIL2 was determined by analyzing both protein and mRNA levels in papillary and micropapillary carcinoma tissues by using immunohistochemistry and real-time PCR methods, respectively. Immunohistochemical analysis of HBME-1, galectin-3 and CK-19 was also performed. Similar to other immune markers of HBME-1, galectin-3 and CK-19, protein expression levels of PIWIL2 was significantly up-regulated in both papillary and micropapillary thyroid cancers (p 0.01). Moreover, consistent with protein expression levels, mRNA expression levels of PIWIL2 was elevated in both papillary and micropapillary thyroid cancer tissues. Yet, mRNA expression changes were statistically insignificant. In conclusion, results of the current study suggest that PIWIL2 can be involved in thyroid cancer tumorigenesis and can be used as a novel predictive biomarker and/or therapeutic target.

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.

Background/aim: To determine the roles of hepcidin and its related genes in a renal ischemia/reperfusion model. Materials and methods: A total of 20 Wistar albino rats were equally divided into 2 groups: Group I was the control group and Group II was the ischemia and reperfusion (I/R) group (60 min of ischemia + 48 h of reperfusion). I/R was performed on the left kidneys of these rats and then the I/R-treated kidneys were removed. The levels of serum biochemical markers were evaluated after renal I/R. The expression levels of hepcidin-linked genes [growth differentiation factor 15 (GDF-15), bone morphogenetic protein 6 (BMP6), and hemojuvelin (HJV)] were also measured by RT-PCR technique. In addition, the tissues were evaluated histopathologically. Results: No significant association was found between renal dysfunction and I/R when compared to biochemical parameters (P > 0.05). However, differences in platelet values were statistically significant (P < 0.05). Expression levels of GDF-15, BMP6, and HJV genes increased, but this increase was not statistically significant. In addition, histopathological evaluation was performed using hematoxylin and eosin stain. This showed a significant relationship between the control group and I/R group for ischemic and nonischemic kidney scoring. Conclusion: Hepcidin and BMP6, HJV, and GDF-15 should be taken into account when investigating the process of I/R.

Breast cancer is major public health problem predominantly effects female population. Current therapeutic approaches to deal with breast cancer are still lack of effectiveness. Thus, identifying/developing novel strategies to fight against breast cancer is very important. The frequent deletions at 8p21.3-22 chromosomal location nearby D8S254 marker enabled the discovery of a novel tumor suppressor gene, MTUS1. Subsequently, MTUS1 was demonstrated to be less expressed in a variety cancer types including breast cancer. Also, it is obvious that gene expression is widely regulated by miRNAs. Here, we aimed to report differential expression of MTUS1 and its regulatory miRNAs in breast cancer and fibroadenoma tissues. Dynamic analysis of MTUS1 expression levels and its miRNAs regulators were attained by Fluidigm 96×96 Dynamic Array Expression chips and reactions were performed in Fluidigm BioMark™ HD System qPCR. Consequently, MTUS1 mRNA levels were significantly diminished in breast cancer tissues and elevated in fibroadenoma tissues. Also, among MTUS1 targeting miRNAs, miR-183-5p was identified to be overexpressed in breast cancer and down-regulated in fibroadenoma tissues. Also, expression levels of MTUS1 and miR-183-5p were well correlated with clinical parameters. In particular, MTUS1 expression was found to be diminished and miR-183-5p expression was elevated with the advancing stage. In conclusion, as a potential therapeutic target, miR-183-5p can be a chief regulator of MTUS1 and MTUS1-miR-183-5p axis may have significant influence in the pathology of breast cancer.

Long non-coding RNAs (lncRNAs) are found to play crucial roles in several biological processes and have been associated with many complex human diseases including cancers. Several lines of evidences indicate that lncRNAs deregulated in many cancer tissues. In this particular study, differential expression of long intergenic non-coding RNA 663 (LINC00663) was demonstrated in various cancer cell lines and healthy human tissues by using RT-PCR and qPCR methods. While expression level of LINC00663 was most prominent in thyroid gland and uterus, it is least expressed in skeletal muscle tissues. Moreover, LINC00663 was found to be differentially expressed in various cancer cells. Particularly, its expression was highly diminished in DU-145, PC3, HGC-27, CRL-1469, A549, MCF7, and BCPAP cancer cells. Also, LINC00663 expression was most prominent in A172 glioblastoma cells. Additionally, a novel splice variant of LINC00663 RNA was also detected. The sequence and Basic Local Alignment Search Tool (BLAST) analysis results revealed the presence of a novel exonic region between exons 2 and 3. Subsequently, five potential splice variants showing high level of variation have been identified. Secondary structures of these variants with minimum free energy were also demonstrated. Furthermore, putative microRNA (miRNA) binding sites to these variants have been shown. In conclusion, LINC00663 was shown to be differentially expressed in various human tissues and cancer cell lines. Also, LINC00663 undergoes alternative splicing and the novel exonic region alters its secondary structure and its interactions with potential targeting miRNAs. The role of LINC00663 in cancer formation further needs to be investigated with a wide range of studies.

Uridine 5′-diphospho-glucuronosyltransferases (UGT) are the key players in the biotransformation of drugs, xenobiotics, and endogenous compounds. Particularly, UDP-glucuronosyltransferase 1A (UGT1A) participates in a wide range of biological and pharmacological processes and plays a critical role in the conjugation of endogenous and exogenous components. Thirteen alternative splicing products were produced from UGT1A gene locus designated as UGT1A1 and UGT1A3–10. A growing amount of evidence suggests that they have important roles in the carcinogenesis which is well documented by colon, liver, pancreas, and kidney cancer studies. Here, we report differential expressions of UGT1A genes in normal and tumor tissues of stomach cancer patients. Total numbers of 49 patients were enrolled for this study, and expression analysis of UGT1A genes was evaluated by the real-time PCR method. Accordingly, UGT1A1, UGT1A8, and UGT1A10 were found to be upregulated, and UGT1A3, UGT1A5, UGT1A7, and UGT1A9 were downregulated in stomach tumors. No expression changes were observed in UGT1A4. Also, UGT1A6 transcription variants were significantly upregulated in stomach cancer tissues compared to normal stomach tissue. Additionally, UGT1A7 gene showed highest expression in both normal and tumoral tissues, and interestingly, UGT1A7 gene expression was significantly reduced in stage II patients as compared to other patients. In conclusion, UGT1A genes are differentially expressed in normal and tumoral stomach tissues and expression changes of these genes may affect the development and progression of various types of cancer including the cancer of the stomach.

0000-0001-8252-3339 WOS: 000356979700010 PubMed ID: 25925209 Colorectal cancer is one of the frequently seen malignancies in the world. To date, several oncogenes and tumor suppressor genes have been identified and linked to colorectal cancer pathogenesis. Although recent advances in the diagnosis and therapy of colorectal cancer are promising, identifying novel genetic contributors is still high priority. In the present study, expression profile of some cancer-related genes and their regulatory miRNA molecules were evaluated by using a high-throughput real-time PCR method. For the study, a total of 54 patients diagnosed with CRC and normal colon tissue samples of 42 healthy controls were included. For the expression analysis, total RNA was extracted from FFPE tissue samples and converted to cDNA. All expression analyses were assessed by using Fluidigm Microfluidic Dynamic Array chips for 96 samples and the reactions were held in Fluidigm BioMark (TM) HD System Real-Time PCR. As a result of the study, expression of the ADAMTS1, FHIT, RUNX1, RUNX3 and WWOX genes was shown to be significantly altered in CRC tissues in contrast to normal tissue samples. Moreover, miR-378a-3p, miR-155-5p, miR-193b-3p, miR-96-5p, miR-17-5p, miR-27a-3p, miR-133b, miR-203a, miR-205-5p, miR-34c-5p, miR-130a-3p, miR-301a-3p, miR-132-3p, miR-222-3p, miR-34a-5p, miR-21-5p, miR-29a-3p and miR-29b-3p were found to be significantly deregulated in CRC. Consequently, results of the current study strongly suggest the involvement of novel cancer-related genes and their regulatory miRNAs in CRC physiopathology. (C) 2015 Elsevier B.V. All rights reserved. Scientific Research Projects Management Unit of Mugla Sitki Kocman UniversityMugla Sitki Kocman University [13/152] This study was supported by a project from the Scientific Research Projects Management Unit of Mugla Sitki Kocman University (Grant number: 13/152).

The breast cancer is one of the most common types of cancer. Many scientists have focused on the treatment of this disease for a long time by studying anti-cancer activities of plant extracts as well as synthetics. Lamiaceae and Asteraceae have been used in anticancer studies due to their phytochemical content. The genus Sideritis, Achillea and Tanacetumare the members of these families. Sideritis, Achillea and Tanacetum are used as herbal medication for the treatment ofvariety of diseases. In present study, we demonstrated the biological activity of Sideritis syriaca (SS), Achillea aleppica (AAZ) and Tanacetum argenteum (TAA) methanol extracts on cell viability of the breast cancer line MCF7. MTT (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to determine the cell viability and proliferation of MCF7 cells. In a dose dependent manner, methanol extracts (0, 1, 5, 25, 100 and 250 µg/ml) of SS, AZZ and TAA were examined on MCF7, and viability of cells were determined with MTT staining. Especially, concentrations in 100 and 250 µg/ml of extracts decreased the cell viability (p

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.

There is very little work on the expression of TRPM6/7 in ischemia reperfusion models. In previous studies, after ischemia, reperfusion had been kept limited to 24 h, yet in our study, expressions of these channels were elucidated after its modification to 48 h to establish what kind of changes renal tissues undergo. For the current study, 20 Wistar albino rats were divided into two groups equally. Group I: control group, Group II = I/R group (60 min ischemia + 48 h reperfusion). For the mRNA analysis, right kidneys of I/R group was used as a reference in order to eliminate genetic differences. The left renal artery (I/R generated part) of I/R area was removed from all rats in the second group. Likewise, normal tissues of right renal artery were removed from all rats. Histopathologic scoring of the tissue samples were achieved semi-quantitatively according to normal tissue composition. Consequently, both TRPM6 and TRPM7 expression levels were decreased in all groups according to control groups, yet results were not counted as significant (p > 0.05). Additionally, correlation analysis confirmed these results. Also, I/R performed kidneys had more tissue damage compared to control group. To conclude, our study results suggest that TRPM6/7 expressions may be increased and after 48 h of reperfusion expression levels of these two stored to normal levels. At the same time, damages have occurred in renal tissues after ischemia. These damages were considered to be resulted from the oxidative effects as previously reported.

513 Background: Different factors are effective in the development of colorectal cancer (CC). With the discovery of that TRP (transient receptor potential) genes family is an important component of calcium channel, about 30 members of the family of TRP ion channel in mammals have been determined up to the present. TRP channels are associated with many pathological conditions like cancer and cardiovascular diseases as well as the physiological significance of them.. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CC patients and to analyze the relationship of expression in tumor tissue of colorectal cancer with other known prognostic factors. Methods: In this study, 93 CC patients whose follow-up and treatment realized in Medical Oncology Department of Gaziantep University Medical Faculty Hospital were analyzed retrospectively. Level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples of 93 patients were studied at the level of mRNA with real-time PCR. Results: From normal and cancerous colorectal tissues of 37 female and 56 male patients diagnosed with colorectal cancer, expressions of TRPV3, TRPV4, TRPV5, TRPM4, and TRPC6 genes in tumor tissue were detected lower when compared to normal tissue (p < 0.05). When expression levels of other TRP genes in tissues were compared, any significant difference was not found (p > 0.05). There was no meaningful difference between prognostic factors and gene expressions of tumor tissues statistically (p > 0.05). Conclusions: Expression of many proteins in cancer cells compared to normal cells increases or decreases. In CC, TRPV3, TRPV4, TRPV5, TRPM4, and TRPC6 genes of which expression in cancerous tissue decreases may be thought as potential genes contributing to tumorigenesis. To verify this hypothesis, it should be supported with further studies.

Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. Material and Methods: In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. Results: The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. Conclusions: TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues. Key Words: colorectal cancer, TRP genes family: TRPV3, TRPV4, TRPV5, TRPM4, TRPC6, mRNA expression.