The expression profile of HAR1A and HAR1B in the peripheral blood cells of multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system (CNS) with varying degrees of axonal and neuronal damage. The onset and progression of the disease are influenced by several environmental and genetic variables. Long non-coding RNAs (lncRNAs) have a crucial role in the pathophysiology of MS. Our study aimed to assess the levels of HAR1A and HAR1B lncRNA expression in the blood samples of MS patients and investigate the relationship between these lncRNAs and disease activity. METHODS AND RESULTS: The blood samples of 100 MS patients, including 82 relapsing-remitting (RR), 8 primary progressive (PP), and 10 secondary progressive (SP) MS cases, and 100 healthy controls were collected. Quantitative real-time PCR was used for the evaluation of gene expression. ROC curve analysis was performed to evaluate the diagnostic potential of lncRNA levels. A significant decrease was detected in HAR1A expressions (P < 0.0001), and a moderate increase was also shown in HAR1B of SPMS patients (P value = 0.0189). HAR1A showed different expression levels in patients over forty (P value = 0.034). The expression levels of HAR1A and HAR1B were positively correlated in MS patients (r = 0.2003, P value = 0.0457). In addition, ROC curve results suggested that HAR1A can be introduced as a novel biomarker for MS diagnosis (AUC = 0.776). CONCLUSION: The low serum level of HAR1A may be a potential molecular biomarker for MS diagnosis; however, no discernible difference was detected in the expression level of HAR1B in the blood samples of MS patients.

Structure-based investigation of rat aldehyde oxidase inhibition by flavonoids.

1. Flavonoids are a group of polyphenolic plant metabolites most commonly known for their antioxidant activities. They also show inhibitory activities on molybdo-flavoenzymes family of enzymes which are involved in biotransformation of some exogenous and endogenous chemicals. Most notably, aldehyde oxidase (AO), a member of this family, is responsible for metabolism of some therapeutic agents. On the other hand, there are some therapeutics which inhibit AO. As flavonoids are ubiquitous in human diet and have potential to interact with AO, it is important to investigate their effects at the molecular details. 2. The inhibitory effects of 15 flavonoids on the activity of rat liver AO were assessed. Quantitative structure-activity relationship studies were performed using genetic algorithm coupled partial least square and stepwise multiple linear regression methods to elucidate the important structural properties responsible for the observed inhibitory effects. To further understand the mode of interaction between these flavonoids and AO, a homology model of the enzyme was built and flavonoids were docked into its active site. The most important amino acids involved in the interactions were identified. 3. Quercetin, myricetin and genistein were the most potent inhibitors establishing favorable interactions with the enzyme. However, the glycosylated flavonoids showed relatively weaker inhibition which may be attributed to their hindered binding into the active site of AO by bulky sugar groups.

Circulating miR-21 and miR-155 as potential noninvasive biomarkers in Iranian Azeri patients with breast carcinoma.

BACKGROUND: Breast cancer (BC) is the most common cause of cancer-related mortality among women. Despite recent advances in diagnosis and prognosis of breast carcinomas, noninvasive biomarkers have been poorly identified. We evaluated the biomarker potential of miR-21 and miR-155 in tissue and plasma specimens of Iranian Azeri patients. MATERIALS AND METHODS: Tumor specimens, paired nontumoral adjacent tissues, and matched plasma samples were collected from a number of thirty Iranian Azeri women with breast carcinoma. Plasma of healthy women was used as the control. The relative expression of miR-21 and miR-155 was measured by real-time polymerase chain reaction. RESULTS: Our data revealed that the expression levels of miR-21 and miR-155 in tumor tissues are significantly higher than paired nontumoral adjacent specimens (P < 0.05). Furthermore, receiver operating characteristic (ROC) curve analysis of samples showed the area under the ROC curve of 0.81 for miR-21 and area of 0.83 for miR-155. In addition, statistical analysis showed that miR-21 and miR-155 RNAs are significantly detected in the plasma of BC patients compared to healthy specimens (P < 0.05). Circulating miRNAs yielded area under the ROC curve of 0.99 for miR-21 and 0.92 for miR-155. CONCLUSION: Our data showed that miR-21 and miR-155 oncomiRs can be considered as noninvasive biomarkers for monitoring breast carcinomas. However, further investigations are needed to confirm the use of these noncoding RNAs in pathology.

Senescence is delayed by selenium in oilseed rape plants.

Leaf senescence is a genetically programmed process that can also be induced by nitrogen (N) deficiency. Although selenium (Se) delays leaf senescence, the underlying mechanisms are still unknown. To explore the mechanisms of Se-mediated delay of leaf senescence, we studied the biochemical and molecular events that occur during developmental and N deficiency-induced senescence. Oilseed rape (Brassica napus L.) plants were grown under adequate N (AN, 16 mM) or low N (LN, 4 mM) conditions during the rosette growth stage and treated with Se (15 µg plant-1 as Na2SeO4) either through roots or leaves for four weeks. Shoot dry matter production was not influenced, while the photosynthetic parameters were improved by Se application in both young and old leaves under both AN and LN conditions. The Se treatment rarely influenced the concentrations of reactive oxygen species (ROS), while it increased the nitric oxide (NO) levels in young and old leaves under both AN and LN conditions. The positive correlation between the NO level and leaf photosynthetic parameters in old leaves of LN plants suggested a role for NO boosting, mediated by Se, in the protection of aging leaves from LN-induced accelerated senescence. This implication was further supported by the clear down-regulation of SAG12-1 and up-regulation of Cab, particularly by root application of Se in old leaves of LN plants. Our results provide the first evidence that Se influences the expression of senescence-associated genes and delays senescence through NO signalling but is independent of the ROS defence system.

Investigation of the changes in the expression levels of MOZ gene in colorectal cancer tissues.

BACKGROUND: MOZ is one of the most important histone acetyltransferases (HATs) that has an effective role in gene expression. It is an important partner in chromosomal rearrangement that usually occurs in hematological malignancies such as leukemia. Besides these malignancies, its role in solid tumors has been reported. In the present study, we aimed to quantify of MOZ messenger RNA (mRNA) expression in colorectal cancer (CRC) tissues from a northwest population of Iran and consequently to assess the effect of MOZ in CRC. METHODS: Tumorous and adjacent non-tumorous tissues recruited from 26 patients with CRC. mRNA extraction and complementary DNA (cDNA) synthesis were performed from these tissues, at the next step quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) was carried out. Finally, expression levels were statistically analyzed using IBM SPSS Statistics 24.0 software and independent t-test. Statistical significance was considered as P≤0.05. RESULTS: The results showed significantly higher expression of MOZ in the majority of CRC tissues compared to normal colorectal tissues (P=0.048). There were no significant correlations between expression levels of MOZ and clinical parameters of patients (P>0.05). CONCLUSIONS: Our data showed that dysregulation of MOZ is potentially involved in the pathogenesis of CRC and we could suggest that there is a straight relationship between tumor formation and MOZ expression. These results showed possible role of MOZ as a prognostic factor in the said population.

Dysregulated KDR and FLT1 Gene Expression in Colorectal Cancer Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly-diagnosed malignancies throughout the world and the fourth-leading cause of cancer deaths globally. Angiogenesis and the resultant tumor neovascularization is a well-known cancer hallmark. Here we investigated the expression of FLT1 and KDR, the influential genes in angiogenesis regulation, in CRC patients. METHODS: We assessed FLT1 and KDR mRNA expression in 47 CRC samples and matched adjacent noncancerous tissues (ANCT) by quantitative real-time PCR. The Spearmen correlation coefficient and receiver operating characteristic (ROC) curves were also examined. RESULTS: Both genes were expressed at significantly greater levels in CRC tissues than in ANCT (p < 0.05). A significant association was found between KDR expression and disease stage and lymph status in CRC patients. Furthermore, the Spearman correlation demonstrated a moderate correlation between FLT1 and KDR expression in CRC samples. Finally, ROC curve analysis demonstrated that FLT1 had the greatest sensitivity (85.1%), while the greatest specificity was achieved by a combination of the two genes. CONCLUSION: The dysregulated FLT1 and KDR expression, in addition to the observed correlation and ROC curve results, indicate the critical importance of angiogenesis among the cancer pathways in CRC. These data can broaden our current knowledge of angiogenesis in CRC to improve disease diagnosis and patient treatment.

Study of cofilin 1 gene expression in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Cofilin is a key regulatory protein in the dynamics of actin filaments. Previous studies have shown cofilin 1's major role in cell migration process and its role in tumor cell migration and invasion. Therefore, cofilin 1 may have the potential as a novel diagnostic tumor marker in various cancers. In this study, differential expression of CFL1 in CRC tissues in comparison with adjacent non-tumor tissues was investigated and the diagnostic value of this protein in CRC was evaluated. METHODS: Synthesized cDNA from extracted RNAs of 30 patients were subjected to qRT-PCR to quantify relative expression of cofilin 1. The relationship between cofilin 1 expression and clinicopathological features of patients were studied too. RESULTS: The study showed significant upregulation of cofilin 1 in CRC tissue samples compared to adjacent non-tumor tissue samples (P<0.05). The receiver operating characteristic curve analysis showed higher area under the curve (0.85). There was no significant correlation between cofilin 1 expression levels and clinicopathological features of patients. CONCLUSIONS: According to the obtained results, cofilin 1 can serve as a candidate for clinically useful diagnostic biomarker or therapeutic target for CRC.

Lack of Associations of the MDM4 rs4245739 Polymorphism with Risk of Thyroid Cancer among Iranian-Azeri Patients: a Case-Control Study

Background and Aim: MDM4, a negative regulator of the p53 tumor suppression pathway, has been demonstrated to be overexpressed in a variety of human cancers. Research has revealed that the rs4245739 A>C polymorphism of MDM4 in the 3'-untranslated region makes it a miR-191 target site, leading to lower MDM4 expression. This study aimed to detect if the rs4245739 single nucleotide polymorphism (SNP) impacts on thyroid cancer (TC) development in Iranian-Azeri patients. Materials and Method: Blood samples were taken from 232 healthy controls and 130 TC patients of Iranian-Azeri ethnicity. For genotyping, Tetra-ARMS PCR was performed. SPSS for Windows (version 22.0, IBM SPSS Inc., USA) and the SHEsis online software were used for data analysis. Results: Alleles of MDM4 rs4245739 SNP demonstrated no significant different in frequencies between patients and controls (p>0.05). Additionally, genotypes of MDM4 rs4245739 SNP did not increase or decrease TC risk in patients compared with healthy subjects. Conclusion: Considering the lack of any observed association between the MDM4 rs4245739 polymorphism and TC, we conclude no significant role in the pathophysiology of the disease.

mRNA expression of nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors in colorectal carcinoma.

Transcription factors are involved in cell cycle and apoptosis regulation and thus have a key role in the carcinogenesis of different tumors. Nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors are important in the carcinogenesis of colorectal cancer (CRC). In this study, we examined whether the expression of NFATc2 and PPARG genes is significantly altered during the carcinogenesis of CRC. A total of 47 tumor samples and matched normal tissue margins were collected during surgery from patients with CRC. In addition, three CRC cell lines (HCT119, SW480, and HT29) and healthy cell line were used. After total RNA extraction and cDNA synthesis, mRNA expression levels of NFATc2 and PPARG were examined by real-time polymerase chain reaction. The results showed that NFATc2 is overexpressed in the tumor tissues compared with normal tissue margins (p ≤ 0.05). However, the mRNA expression levels of PPARG were not significantly different between the tumor tissues and tissue margins. Our results indicate that NFATc2 may be used as an early diagnostic or predictive biomarker for CRC as well as a therapeutic target, providing that upcoming studies confirm these results.