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Cell Journal [Yakhteh]. 2019; 20 (4): 564-568
in English | IMEMR | ID: emr-199627


Objective: Considerable research shows that long non-coding RNAs, those longer than 200 nucleotides, are involved in several human diseases such as various cancers and cardiovascular diseases. Their significant role in regulating the function of endothelial cells, smooth muscle cells, macrophages, vascular inflammation, and metabolism indicates the possible effects of lncRNAs on the progression of atherosclerosis which is the most common underlying pathological process responsible for coronary artery disease [CAD]. The aim of present study was to assess whether the expression of the lnc RNA H19 was associated with a susceptibility to CAD by evaluating the expression level of H19 in the peripheral blood

Materials and Methods: A case-control study of 50 CAD patients and 50 age and sex-matched healthy controls was undertaken to investigate whether the H19 lncRNA expression level is associated with a CAD using Taqman Real-Time polymerase chain reaction [PCR]

Results: The subsequent result indicated that the H19 lncRNA was over-expressed in CAD patients in comparison with the controls. However, it was not statistically significant. This overexpression may be involved in coronary artery disease progression

Conclusion: We report here, the up-regulation of H19 lncRNA in the whole blood of CAD patients and suggest a possible role for H19 in the atherosclerosis process and its consideration as novel biomarker for CAD

IBJ-Iranian Biomedical Journal. 2018; 22 (4): 231-236
in English | IMEMR | ID: emr-199445


Background: Telomeres are evolutionary, specialized terminal structures at the ends of eukaryotic chromosomes containing TTAGGG repeats in human. Several human diseases have been known to be associated with dramatic changes in telomere length. The aim of the present study was to assess the correlation between the relative leukocyte telomere length [LTL] and infertility in a group of Iranian azoospermic males

Methods: In this casecontrol pilot study, relative telomere length [RTL] of peripheral blood leukocytes from a total of 30 idiopathic nonobstructive azoospermic males and 30 healthy fertile males was evaluated using real-time PCR. RTL was calculated as T [telomere]/S [single copy gene] ratio and compared between infertile and fertile groups

Results: Patients with azoospermia showed significantly shorter RTL than fertile males [0.54 vs. 0.84, p < 0.05]. The area under the receiver operating characteristic [ROC] curve was estimated to be 99.8%, suggesting LTL as a potential marker for the diagnosis of azoospermia

Conclusion: Our findings demonstrated a probable association between telomere shortening and azoospermia in a population of Iranian infertile men affected by idiopathic azoospermia

IBJ-Iranian Biomedical Journal. 2017; 21 (5): 303-311
in English | IMEMR | ID: emr-188487


Background: Colon cancer-associated transcript 2 [CCAT2] is a newly recognized IncRNA transcribed from the 8q24 genomic region. It functions as an oncogene in various types of cancers including breast cancer, in which it affects Wnt/p-catenin pathway. Previous studies have shown a putative interaction between this IncRNA and MYC proto-oncogene

Methods: In the current study, we evaluated the expression of CCAT2 in breast cancer tissues with regards to the expression of its target MYC. In addition, we assessed the relationship between CCAT2 and MYC expression levels in tumor tissues and the clinical prognostic characteristics of breast cancer patients

Results: MYC expression levels were significantly up-regulated in tumor tissues compared with adjacent non-cancerous tissues [ANCTs], while such analysis showed no statistically significant difference between these two tissue types in CCAT2 expression. Starkly increased CCAT2 gene expression levels were found in 12/48 [25%] of cancer tissue samples compared with their corresponding ANCTs. Furthermore, significant inverse correlations were found between CCAT2 expression and stage, as well as lymph node involvement. Besides, a significant inverse correlation was found between the relative MYC expression in tumor tissues compared with their corresponding ANCTs and disease stage

Conclusions: These results highlight the significance of MYC and CCAT2 expressions in the early stages of breast cancer development and suggest a potentially significant role for CCAT2 in a subset of breast cancer patients, which could be applied as a potential therapeutic target in these patients

Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Genes, myc , RNA, Long Noncoding , Lymph Nodes/pathology , Gene Expression , Iran
Cell Journal [Yakhteh]. 2016; 18 (2): 237-244
in English | IMEMR | ID: emr-183014


Objective: Hypoxia-Inducible Factor [HIF]-1 plays an essential role in the body's response to low oxygen concentrations and regulates expression of several genes implicated in homeostasis, vascularization, anaerobic metabolism as well as immunological responses. Increased levels of HIF-1alpha are associated with increased proliferation and more aggressive breast tumor development. Lactobacilli have been shown to exert anti-cancer effects on several malignancies including breast cancer. However, the exact mechanism of such effect is not clear yet. The aim of this study was to analyze the expression of selected genes from HIF pathway in a triple negative breast cancer cell line [expressing no estrogen and progesterone receptors as well as HER-2/Neu], MDA-MB-231, following treatment with two lactobacilli culture supernatants

Materials and Methods: In this experimental study, we analyzed the expression of HIF-1alpha, SLC2A1, VHL, HSP90, XBP1 and SHARP1 genes from HIF pathway in MDA-MB-231 cells, before and after treatment with Lactobacillus crispatus and Lactobacillus rhamnosus culture supernatants [LCS and LRS, respectively] by means of quantitative reverse-transcription polymerase chain reaction [qRT-PCR]

Results: Both LRS and LCS had cytotoxic effects on MDA-MB-231 cells, while the former type was more cytotoxic. LRS dramatically down-regulated expression levels of the HIF-1alpha, HSP90 and SLC2A1 in the MDA-MB-231 cells. LCS had similar effect on the expression of HSP90, to what was observed in the LRS treatment. The expression level of tumor suppressor genes VHL and SHARP1 were also decreased in LCS treated cells

Conclusion: Although both LCS and LRS had cytotoxic effects on the MDA-MB-231 cells, it is proposed that LRS could be more appropriate for pathway directed treatment modalities, as it did not decrease expression of tumor suppressor genes involved in HIF pathway. Down-regulation of HIF pathway mediated oncogenes by LRS suggests that the cytotoxic effects of this Lactobacillus may at least be partly caused by this mechanism. As previous studies have shown that inhibition of HIF-1alpha and HSP90 expressions have therapeutic impact on cancer treatment, the inhibitory effect of LRS on expression of these genes implies that this Lactobacillus can be used in treatment strategies

Novelty in Biomedicine. 2016; 4 (4): 173-180
in English | IMEMR | ID: emr-184186


Background: Type II diabetes is known as one of the most important, prevalent, and expensive diseases of mankind. Late diagnosis and subsequent delayed initiation of treatment or surveillance of patients create a variety of problems for affected individuals. This has raised increasing concerns for public health authorities throughout the world. In the current study, we aimed to find a new approach for early identification of high-risk individuals at initial months of their life. This allows us to take preventive measures as early as possible

Materials and Methods: In our study, 102 infants - from one to six months - were selected and placed in two case and control groups. The case group contained 52 babies with at least one of their parents identified as a type II diabetic patient. The control group comprised 50 babies with no family history of type II diabetes in paternal and maternal first-degree relatives. Afterwards, the expression level of insulin gene was analyzed in white blood cells of both groups. Information related to infants - referred to outpatient and inpatient wards of three main pediatric hospitals placed in Tehran - and their parents were collected through questionnaires within a two-year period. The study inclusion criteria for infants were confirmed type II diabetes in at least one of their parents, the absence of any metabolic disorder, and the absence of any disturbing vital signs. After drawing 2 ml of babies' peripheral blood, total RNA of white blood cells [WBC] was extracted, and used for cDNA synthesis. Real-Time PCR was then applied to quantitatively evaluate the expression levels of insulin gene. The results of Real-Time PCR were statistically analyzed by non-parametric tests of Mann-Whitney and Kruskal-Wallis

Results: The expression of insulin gene was observed in white blood cells of all samples. However, there was a significant difference in expression levels between case and control groups [p<0.05]. There was a statistically significant difference in mean levels of gene expression among babies with diabetic mother, and healthy groups [RQ=0.5, P-value=0.002], but this value wasn't significant for babies with diabetic father [RQ=0.78, P>0.05]

Conclusion: Numerous genes contribute to the development of diabetes and novel disease-causing genes are increasingly being discovered. Identification of disease-prone individuals through examining merely one underlying gene is complicated and challenging. Interestingly, all of these abnormally functioning genes finally manifest themselves in the altered expression levels of insulin gene. The expression status of insulin gene in WBCs could be suggested as a useful approach for identification of individuals at high risk for developing diabetes. This paves the way for taking appropriate measures at infancy period in order to prevent the disease as well as inhibit its various side effects in the following years of patient's life

IJRM-Iranian Journal of Reproductive Medicine. 2014; 12 (5): 313-320
in English | IMEMR | ID: emr-147748


The Wnt/beta- The Wnt/beta-catenin signaling pathway is involved in many developmental processes in both fetal and adult life; its abnormalities can lead to disorders including several types of cancers and malfunction of specific cells and tissues in both animals and humans. Its role in reproductive processes has been proven. This study was designed to evaluate the expression of the key regulator of this signaling pathway GSK3-beta and its presumed role in azoospermia. WNT3[a] protein concentration and GSK3-beta gene expression levels were measured and compared between two groups of infertile men. The test groups consisted of 10 patients with obstructive and 10 non-obstructive azoospermia. The control group was selected among healthy men after vasectomies that were willing to conceive a child using a testicular biopsy technique. Samples were obtained by testicular biopsy and screened for the most common mutations [84, 86 and 255] in the SRY region before analyzing. GSK3-beta gene expression was assessed quantitatively by real time-PCR. The WNT3[a] protein concentration had no significant difference between the two test groups and controls. Expression of GSK3-beta was down-regulated in non-obstructive azoospermia [3.10 +/- 0.19] compared with normal [7.12 +/- 0.39] and obstructive azoospermia [6.32 +/- 0.42] groups [p=0.001]. Down-regulation of GSK-3beta may cause to non-obstructive azoospermia. Regulation and modification of GSK-3beta gene expression by drugs could be used as a therapeutic solution