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Long non-coding RNAs (lncRNAs) influence pathetiology of breast cancer. Besides, VDR and ESR1 signaling pathways are two important pathways in this malignancy. In the present mixed bioinformatics and expression assay study, we have identified lncRNAs that are co-expressed with VDR and ESR1 in breast cancer tissues and analyzed their expression in 42 paired breast cancer and non-cancerous specimens. Expression of SLC16A-AS1 was significantly lower in breast cancer tissues compared with paired non-cancerous samples (expression ratio = 0.27, P value < 0.001). Similarly, LINC00900 was down-regulated in cancer tissues compared with non-cancerous ones (expression ratio = 0.26, P value = 0.01). There were no significant differences in the expressions of VDR and AATBC between these two sets of samples. Expression levels of VDR and AATBC were associated with histological grade (P values = 0.02 and 0.03, respectively). Moreover, expression of VDR was associated with tumor size (P value = 0.02). Finally, expression levels of SLC16A-AS1 were associated with first pregnancy age (P value = 0.006). In brief, the results of current study further support involvement of VDR and ESR1-associated lncRNAs in breast cancer.

Purpose Gastric cancer (GC) as a multifactorial disease is caused by environmental, infectious, and genetic factors. The aberrant expression of lncRNAs has been considered as a crucial feature of human cancer. In this research, we assessed the expression levels of a linc00659 in GC patients.Methods Expression of linc00659 in tumor and non-tumor tissues (a total of 82 samples) was evaluated using qRT-PCR in Iranian patients. The correlation between the linc00659 expression levels and clinicopathological features was assessed.Results Linc00659 was down-regulated in more GC samples compared to controls, but we found no significant association between the linc00659 expression levels and GC risk [expression ratio of linc00659 in tumor tissues versus non-tumor tissues was 0.57 (p = 0.33)]. After classifying patients into down−/up-regulation groups, a significant association was observed between the linc00659 expression and origin of the tumor (p = 0.01).Conclusion We found a significant association of the linc00659 expression with origin of the tumor. Further investigations with large sample size are required to assess the linc00659 function in tumor genesis.

MALAT1 is a long non-coding transcript that affects immune reactions, thus being involved in the pathoaetiology of immune-related conditions. We investigated the associations between two genetic variants in MALAT1 and susceptibility to psoriasis in the Iranian population. The G allele of rs619586 has been shown to be less common among cases versus controls (odds ratios (OR; 95% confidence intervals (CI)) = 0.57 (0.36-0.9)), adjusted p = .02). This single nucleotide polymorphism has been associated with the risk of psoriasis in a dominant model (AG + GG vs. AA: OR (95% CI) = 0.56 (0.35-0.92), adjusted p = .04) as well as log-additive model (OR (95% CI) = 0.59 (0.38-0.92), adjusted p = .04). The rs3200401 was not associated with psoriasis in any of the supposed inheritance models. This study potentiates rs619586 as a risk locus for psoriasis in the Iranian population.

Obsessive-compulsive disorder (OCD) is a complex multi-gene disorder. In the current study, we genotyped six single nucleotide polymorphisms (SNPs) within MOCOS, NINJ2 and AKT1 genes in a cohort of Iranian patients with this disorder and healthy controls. C allele of rs1057251 has been found to increase risk of OCD (OR (95% CI) =6.39 (4.64-8.79), P value

Genetic variants within oncogenic long non-coding RNAs HOTAIR and HOTTIP may affect their gene expression levels, thereby modifying genetic susceptibility to gastric cancer (GC). In a hospital-based study in Ardabil—a very high-risk area in North-West Iran, 600 blood samples from 300 GC patients and 300 healthy controls were recruited for genotyping. Seven HOTAIR (i.e., rs17720428, rs7958904, rs1899663, and rs4759314) and HOTTIP (i.e., rs3807598, rs17501292, and rs1859168) ‘tag’ single nucleotide polymorphisms (SNPs) were genotyped by the Infinium HTS platform. The rs17720428, rs7958904, and rs1899663 tagSNPs significantly increased GC risk under dominant models by 1.5-, 1.57-, and 1.5-fold, respectively. The G-C-T-A haplotype of HOTAIR tagSNPs increased the risk of GC by 1.31-fold. No significant association was found between HOTTIP SNPs and the risk of GC. HOTAIR and HOTTIP variants were also not associated with any clinicopathologic characteristics. The SNP-SNP interaction of HOTAIR rs17720428/rs7958904 with HOTTIP rs1859168 was associated with an increased risk of GC (rs17720428 TG-rs1859168 CC, OR = 1.76; rs7958904 GC-rs1859168 CC, OR = 1.85; rs7958904 CC-rs1859168 CC, OR = 1.86). Interestingly, the SNP-SNP interaction of HOTAIR rs1899663 with HOTTIP rs1859168 strongly increased the risk of GC (rs1899663 GT-rs1859168 CC, OR = 4.3; rs1899663 TT-rs1859168 CC, OR = 9.37; rs1899663 TT-rs1859168 CA, OR = 6.59). We showed that the HOTAIR rs17720428, rs7958904, and rs1899663 tagSNPs and their interactions with the HOTTIP rs1859168 polymorphism significantly increased the risk of GC. Specifically, novel SNP-SNP interactions between HOTAIR and HOTTIP tagSNPs have a larger impact than individual SNP effects on GC risk, thereby providing us with valuable information to reveal potential biological mechanisms for developing GC.

Lung cancer as the most common cancer in the world is associated with high rate of mortality. Previous studies have detected expression of vitamin D receptor (VDR) in lung cancer tissues and reported significant of this gene in determination of patients' survival. Methods: In the current study, we assessed expression of VDR and five long non-coding RNAs (lncRNAs) which have been associated with VDR (MALAT1, SNHG16, SNHG6, LINC00346, LINC00511) in 32 pairs of lung cancer tissues and adjacent non-cancerous tissues (ANCTs) using real time PCR method. Expression of VDR was significantly decreased in tumor tissues obtained from male patients compared with their matched ANCTs (ER = 0.31, P value = 0.02). However, this pattern was not detected in female subjects (ER = 0.93, P value = 0.94). Expression of LINC00346 was significantly decreased in tumoral tissues compared with ANCTs (Expression ratio (ER) = 0.38, P value = 0.03). When evaluating expression of this lncRNA based on the sex of patients, differences in its expression was only significant among males (ER = 0.3, P value = 0.04). VDR expression was significantly associated with sex of patients in a way that most male patients exhibited down-regulation of this gene in their tumor tissue samples compared with the paired ANCTs (P = 0.03). Expression levels of LINC00346 could discriminate lung cancer tissues from ANCTs with sensitivity of 83.3% and specificity of 52.4%. Correlations between expressions of SNHG6 and other genes were all significant in tumoral tissues but insignificant in ANCTs. The current investigation potentiates VDR and LINC00346 as possible participants in the pathogenesis of lung cancer.

Suicidal behavior as a psychological problem with high public health burden is associated with a number of genetically determined risk factors. In the current study, we investigated the association between two polymorphisms within the NINJ2 gene and risk of suicide in an Iranian population. The study included 295 individuals who attempted suicide with soft suicide methods, 234 suicide victims and 410 normal controls. The rs11833579 SNP was associated with death from suicide in a codominant model in that the AG genotype decreased the risk of death from suicide compared with the GG genotype (OR (95% CI) = 0.49 (0.34–0.71), adjusted P value = 4e−04). This SNP was also associated with death from suicide in dominant (AG + AA versus GG: OR (95% CI) = 0.63 (0.46–0.87), adjusted P value = 0.011) and overdominant (AG versus GG + AA: OR (95% CI) = 0.49 (0.35–0.69), adjusted P value

Mitogen-activated protein kinase (MAP kinase) pathways participate in regulation of several cellular processes involved in breast carcinogenesis. A number of non-coding RNAs including both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate or being regulated by MAPKs. We performed an in-silico method for identification of MAPKs with high number of interactions with miRNAs and lncRNAs. Bioinformatics approaches revealed that MAPK14 ranked first among MAPKs. Subsequently, we identified miRNAs and lncRNAs that were predicted to be associated with MAPK14. Finally, we selected four lncRNAs with higher predicted scores (NORAD, HCG11, ZNRD1ASP and TTN-AS1) and assessed their expression in 80 breast cancer tissues and their adjacent non-cancerous tissues (ANCTs). Expressions of HCG11 and ZNRD1ASP were lower in tumoral tissues compared with ANCTs (P values < 0.0001). However, expression levels of MAPK14 and NORAD were not significantly different between breast cancer tissues and ANCTs. A significant association was detected between expression of HCG11 and estrogen receptor (ER) status in a way that tumors with up-regulation of this lncRNA were mostly ER negative (P value = 0.04). Expressions of ZNRD1ASP and HCG11 were associated with menopause age and breast feeding duration respectively (P values = 0.02 and 0.04 respectively). There was a trend towards association between ZNRD1ASP expression and patients’ age of cancer diagnosis. Finally, we detected a trend toward association between expression of NORAD and history of hormone replacement therapy (P value = 0.06). Expression of MAPK14 was significantly higher in grade 1 tumors compared with grade 2 tumors (P value = 0.02). Consequently, the current study provides evidences for association between lncRNA expressions and reproductive factors or tumor features.

Introduction: Long non-coding RNAs (lncRNAs) have fundamental roles in cell migration, proliferation, invasion and metastasis. Methods: In the current study, we evaluated expression of a panel of lncRNAs in bladder cancer tissues, adjacent non-cancerous tissues (ANCTs) and normal bladder tissues to evaluate their diagnostic power. Results: PV1 was down-regulated in tumor tissues compared with both ANCTs and normal controls (Expression ratios of 0.48 and 0.14; P values of 0.4 and

Background Proteins encoded by Suppressors of cytokine signaling (SOCS) genes have critical roles in the regulation of immune responses. Meanwhile, several lines of evidence support the presence of immune dysfunction in bipolar disorder (BD) patients. Methods In the present study, we assessed expression levels of SOCS1–3 and SOCS5 genes in peripheral blood of patients with BD and healthy subjects. Results All SOCS genes were up-regulated in patients compared with healthy subjects. However, when comparing patients with sex-matched controls, the significant differences were observed only in the male subjects except for SOCS5 which was up-regulated in both male and female patients compared with the corresponding control subjects. Significant pairwise correlations were found between expression levels of genes in both patients and controls. Based on the area under curve values, SOCS5 had the best performance in the differentiation of disease status in study participants (AUC = 0.92). Combination of four genes increased the specificity of tests and resulted in diagnostic power of 0.93. Conclusion Taken together, these data suggest a role for SOCS genes in the pathogenesis of BD especially in the male subjects. Moreover, peripheral expression levels of SOCS genes might be used as a subsection of a panel of diagnostic biomarkers in BD.

Long non-coding RNAs (lncRNAs) have been identified as modulators of gastric carcinogenesis. Evaluation of expression amounts of these transcripts is a primary but essential step for recognition of the role of lncRNAs in the carcinogenesis. Therefore, we compared expressions of

End-stage renal disease (ESRD) is a public health problem with a high burden. The condition is associated with abnormalities in lipid metabolism. The fatty acid desaturase (FADS) gene cluster includes three genes that are significantly correlated with a number of pathologic conditions related to abnormal lipid levels. In the current study, we genotyped rs174556, rs99780, and rs7115739 single nucleotide polymorphisms within the FADS cluster in a population of ESRD patients and healthy controls. The rs174556 of the FADS1 gene and rs99780 of the FADS2 gene were not associated with the risk of ESRD in any inheritance model. However, the rs7115739 of FADS3 was associated with the risk of ESRD in all models except for the recessive model. The T allele of this SNP was significantly less prevalent among cases compared with controls [odds ratio (OR) (95% CI) = 0.44 (0.25–0.77), P value = 0.004]. GT and TT genotypes has been shown to decrease the risk of ESRD in a codominant model [OR (95% CI) = 0.49 (0.26–0.92) and OR (95% CI) = 0.18 (0.02–1.6), respectively; P value = 0.019]. In the dominant model, GT + TT status was associated with lower risk of ESRD [OR (95% CI) = 0.45 (0.24–0.82), P value = 0.0078]. Assessment of association between this SNP and risk of ESRD in an overdominant model revealed that GT genotype decreases the risk of this condition [OR (95% CI) = 0.5 (0.27–0.94), P value = 0.029]. Taken together, the rs7115739 of FADS3 is suggested as a putative modulator of the risk of ESRD in the Iranian population.

Aim: Protein inhibitor of activated STAT ( PIAS) family includes transcriptional regulator proteins with SUMO E3 ligase activity. They regulate expression of several genes involved in cell proliferation, differentiation and survival. Method: We evaluated expression of PIAS1–4 genes in 54 breast cancer tissues and their paired adjacent noncancerous tissues. Results: PIAS2 and PIAS3 genes were significantly downregulated in tumoral tissues compared with adjacent noncancerous tissues. PIAS1–3 expressions were significantly lower in estrogen receptor (ER+) samples compared with ER- samples while PIAS4 had the opposite trend. PIAS3 expression was significantly higher in grade 1 samples compared with grade 2 samples. Conclusion: These findings highlight the role of PIAS genes in the pathogenesis of breast cancer and their association with determinants of response to antihormone therapies.

The brain-derived neurotrophic factor (BDNF) is a certain type of growth factor that participates in the correct construction of the brain. Moreover, some reports have shown its participation in the tumorigenesis process. A long noncoding RNA known as BDNF-antisense (BDNF-AS) is shown to be transcribed from the antisense direction of the BDNF gene and control its expression. In the current study, we compared expression levels of BDNF and its antisense in gastric cancer tissues and adjacent noncancerous tissues (ANCTs) using quantitative real-time polymerase chain reaction. Expression of both genes tended to decrease in gastric cancer tissues in comparison with ANCTs (expression ratio = 0.4 and P =.06 for BDNF; expression ratio = 0.35 and P =.05 for BDNF-AS, respectively). Relative transcript levels of both genes were remarkably associated with the site of primary tumor in a way that all cardia tumors had low levels of both BDNF and BDNF-AS in comparison with their paired ANCTs (P =.002 and P =

Bipolar disorder (BD) is a chronic, serious mental disorder distinguished by repeated episodes of mania and depression. Previous studies have demonstrated dysregulation of a number of transcripts in brain tissue or peripheral blood of BD patients. In the present study, we compared expression of two protein coding genes (brain-derived neurotrophic factor (BDNF) and beta-secretase 1 (BACE1)) and their natural occurring anti-sense (AS) RNAs (BDNF-AS and BACE1-AS) in peripheral blood of 50 BD patients (mean age ± standard deviation (SD) = 36.5 ± 9.32) and 50 healthy subjects (mean age ± SD = 33.62 ± 8.59). BDNF and BACE1 were significantly up-regulated in peripheral blood of total BD patients compared with total healthy subjects (Expression ratio = 2.2, P value = 0.003; Expression ratio = 2.2, P value = 0.002 respectively). However, comparison of their levels in sex-based subgroups showed their up-regulations only in male patients compared with male health subjects (Expression ratio = 2.48, P value = 0.006; Expression ratio = 2.1, P value = 0.01). No significant differences were found in expressions of BDNF-AS and BACE1-AS between BD and health subjects. We detected a significant correlation between BDNF expression and age at disease onset in BD group after adjustment of the effects of sex (R = 0.26, P value = 0.03). Moreover, there were trends toward correlations between BDNF expression and disease duration in BD group and between BDNF expression and age in health subjects (P values = 0.05). Combination of BDNF, BDNF-AS and BACE1 expression levels could differentiate BD patients from healthy subjects with 68% sensitivity and 82% specificity (area under curve = 0.72, P value = 0.0001). The current study suggests a sex-based dimorphic pattern in expression of BDNF and BACE1. Moreover, our results imply that expression pattern of these genes could be diagnostic markers in BD. Future studies are needed to assess this speculation in larger patient samples. Keywords: Bipolar disorder, BDNF, BDNF-AS, BACE1, BACE1-AS

The long non-coding RNA (lncRNA) DSCAM-AS1 has been demonstrated to participate in the pathogenesis of breast cancer and tamoxifen resistance. OBJECTIVE: To evaluate expression profile of DSCAM-AS1 in invasive ductal carcinoma of breast and its suitability as a biomarker for diagnosis of breast cancer. METHODS: We evaluated expression of DSCAM-AS1 in 108 breast tissues including tumoral and adjacent non-cancerous tissues (ANCTs) by means of quantitative real time PCR. RESULTS: DSCAM-AS1 was up-regulated in tumoral tissues compared with ANCTs (Fold change = 2.86, P = 0.011). Its expression was significantly higher in patients aged less than 55 compared with older patients (P = 0.02). However, its expression levels had not a good performance as a diagnostic biomarker for breast cancer. CONCLUSIONS: The significant up-regulation of DSCAM-AS1 in tumoral tissues compared with ANCTs provides further evidences for participation of this lncRNA in the pathogenesis of breast cancer. © 2019 - IOS Press and the authors. All rights reserved.

Long noncoding RNAs (lncRNA) regulate expressions of several cancer-related genes and pathways. Expression profiling of lncRNAs would pave the way for identification of dysregulated pathways in cancer. We assessed expression of FAS-anti sense 1 (FAS-AS1), Taurine Upregulated 1 (TUG1), OPA-interacting protein 5-AS1 (OIP5 -AS1), nuclear-enriched abundant transcript 1 (NEAT1), and highly upregulated in liver cancer (HULC) in breast tumor tissues and adjacent noncancerous tissues (ANCTs). TUG1 was downregulated in tumoral tissues. We found associations between TUG1 expression and mitotic rate, NEAT1 expression and breast feeding duration as well as FAS-AS1 and OPI5 expressions and menarche age. A combination of transcript levels of all genes had 88.5% sensitivity and 42.3% specificity in breast cancer diagnosis. The current study provides evidence for the contribution of lncRNAs in breast cancer in relation to reproductive factors and tumor characteristics.

Breast cancer as a molecularly heterogeneous disorder harbors dysregulation of several signaling pathways. Estrogen receptor (ER) and vitamin D receptor (VDR) are tow signaling pathways whose fundamental roles in breast cancer have been documented. The presence of a negative vitamin D response element in the Estrogen receptor 1 (ESR1) gene promoter has provided evidences for interactions between ER and VDR signaling pathways. Moreover, recent data indicate that certain long non-coding RNAs (lncRNAs) regulate expression of ER and VDR. In the present study, we conducted an in silico approach for identification of lncRNAs that might affect these two pathways in opposite manners. Subsequently, we assessed the interaction of these lncRNAs with tumor suppressor/oncogenic miRNAs and transcription factors to highlight their importance in the pathogenesis of cancer. The results of the current study propose certain lncRNAs with regulatory roles on both ER and VDR signaling pathways to assess their expression pattern, functional roles and possible therapeutic application in future experiments.

Background The brain-derived neurotrophic factor (BDNF) has been implicated in the pathology of CNS disorders as well as cancer. A long non-coding RNA has been distinguished that is transcribed from the anti-sense (AS) strand of BDNF locus. Method We evaluated expression of BDNF and BDNF-AS in breast cancer and adjacent non-cancerous tissues (ANCTs) using real-time PCR technique. Result Expression of BDNF-AS was associated with both tumor grade and mitotic rate. BDNF expression was significantly lower in estrogen receptor (ER) positive samples compared with ER negative samples. Moreover, significant pairwise correlations were found between expressions of these genes in both tumoral tissues and ANCTs. Conclusion We provided evidences for participation of BDNF and its naturally occurring anti-sense in the pathogenesis of breast cancer.

Aim: miRNAs have been suggested as biomarkers for bladder cancer. We aimed to find a diagnostic panel of miRNAs based on differential expression of miRNAs in urine specimens of patient with bladder cancer compared with control group. Methods: miR-141, miR-10b, miR-34b and miR-103 were selected to assess their expression in urine samples of 66 bladder cancer patients and 53 matched controls using quantitative real time PCR. Results: miR-10b and miR-34b were upregulated in cases compared with controls. The combination of four miRNAs showed a sensitivity of 75% and specificity of 63.5% with a diagnostic power of 72%. Conclusion: Certain miRNAs can be used as biomarkers for early diagnosis of bladder cancer.

Background Bladder cancer (BC) is a frequent cancer with high morbidity and mortality. Method We assessed expression of NMP22, BAG3, BCL2 and BAX in BC samples, adjacent non-neoplastic tissues (ANNTs), urinary cell pellets (UCP) of the same patients and non-malignant conditions (NM). Results NMP22 was up-regulated in tumoral tissues compared with ANNTs and in UCP of BC patients compared with UCP of NM. BCL2 and BAX were down-regulated in BC tissues compared with ANNTs. BAG3 and BAX were down-regulated in UCP of BC compared with NM. The combination of all four genes had 100% sensitivity and specificity for detection of BC in urine. Conclusion Expression analysis of these genes in tumor or urine is a tool for detection of BC.

BACKGROUND: The importance of cancer stem cells (CSCs) in initiation and progression of breast cancer has been well established. This population of cells is characterized by high expression of CD44 and low expression of CD24. OBJECTIVE: However, the relative abundance of CD24 and CD44 transcripts in breast cancer tissues and adjacent non-cancerous tissues (ANCTs) has not been quantified yet. METHODS: In the present investigation, we assessed expression of CD24 and CD44 at transcript level in breast cancer tissues and ANCTs in association with clinical determinants of patients' outcome and parameters that predict response to therapeutic options. RESULTS: There was no significant difference in expression of CD24 and CD44 in breast cancer tissues compared with ANCTs (Expression ratios: 1.03 and 0.84, P values: 0.92 and 0.61, respectively). However, CD44 expression was associated with tumor size in a way this gene was up-regulated in all of small sized (≤2 cm) tumors compared with the corresponding ANCTs (P value = 0.04). Besides, CD44 expression was significantly higher in tumors with extracapsular nodal extension compared with those without extension (P = 0.04). Expression of CD24 was higher in grade 3 tumors compared with grade 2 tumors (P = 0.04). CONCLUSION: Expression levels of CD24 and CD44 were correlated with each other in ANCTs but not in tumoral tissues. The current study shows another aspect of CSC markers in the development of breast cancer. © 2020 - IOS Press and the authors. All rights reserved.

Gastric cancer is a multifactorial malignancy with several risk factors worldwide and over one million new cases in 2018 [1]. Long non-coding RNAs (lncRNAs) are non-coding transcripts of >200 nucle...

Breast cancer as the most common female cancer is a malignancy with heterogeneous course. Dysregulation of several genes has been associated with development of this malignancy. Among these genes are the stem cell markers CD61 and breast cancer resistance protein (BCRP or ATP-binding cassette super-family G member 2 (ABCG2)). ABCG2 is one of the major efflux transporters implicated in multidrug resistance in cancer cells. In the present study, we compared expression of CD61 and ABCG2 transcripts between 30 breast cancer tissues and matched adjacent non-cancerous tissues (ANCTs) using real time qPCR technique. There was no significant difference in expression of CD61 or ABCG2 between tumoral tissues and ANCTs (Expression ratios = 1.21 and 0.98, P values = 0.55 and 0.96, respectively). There was a trend toward association between relative expression of CD61 (tumoral tissues versus ANCTs) and patients’ age (P = 0.05) in a way that older patients tended to over-express this marker in their tumoral tissues compared with the matched ANCTs. Moreover, there was a significant association between expression of this gene and tumor size (P = 0.04) in a way that all tumors with sizes less than 2 cm showed down-regulation of CD61 (as compared with the matched ANCTs). Expression of CD61 was significantly higher in tumor tissues with extracapsular nodal extension compared with confined lesions (P = 0.007). Moreover, expression of ABCG2 was significantly higher in tumor tissues of patients aged less than 55 years compared with older patients (P = 0.04). There was no significant correlation between expression of CD61 and ABCG2 either in tumoral tissues or in ANCTs. The current investigation shows association or trends toward association between expression of two cancer stem cell markers and some clinical data of breast cancer patients such as extracapsular nodal extension, age and tumor size which might imply their importance in the pathogenesis of breast cancer.

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

Aim: The current study aimed to identify the expression levels of SE Translocation (SET), Zinc Finger, and X-Linked Factor (ZFX) in gastric cancer tissues and their corresponding adjacent non-cancerous tissues (ANCTs). Background: SET has been first identified as a component of a fusion protein produced by chromosomal rearrangement in a patient with acute undifferentiated leukemia. Subsequently, multiple functions have been attributed to this gene in different disorders such as cancer and Alzheimer’s disease. The expression of SET is regulated by ZFX, a transcription factor which has a potential role in gastric cancer. Methods: In this case-control study, we evaluated the expression of SET and ZFX in gastric cancer tissues (n=28) and their corresponding ANCTs (n=28) via quantitative real-time PCR. Results: SET1 gene was down-regulated in tumoral tissues compared with ANCTs (expression ratio=0.25, P=0.015). However, the expression of ZFX was similar between tumoral tissues and ANCTs (expression ratio=0.97, P=0.945). We detected a significant association between the site of primary tumor and SET1 relative expression in tumoral tissues versus ANCTs, where this gene was down-regulated in all tumors originating from cardia. Based on the area under the receiver operating characteristic curve, the diagnostic power of transcription levels of SET1 in gastric cancer was 0.68. Finally, we observed remarkable correlations between expression levels of SET1 and ZFX both in tumoral tissues (R2=0.38, P

Vimentin (VIM) is a mesenchymal marker which is expressed in some cancer types including breast cancer. A long non-coding RNA (lncRNA) has been identified to be transcribed from VIM gene locus and positively regulate expression of VIM. This lncRNA has been named as VIM-antisense 1 (VIM-AS1). Expression of VIM is also regulated by another lncRNA namely AGAP2-antisense RNA 1 (AGAP2-AS1). In the current study, we aimed at identification of the expression pattern of VIM, VIM-AS1, AGAP2 and AGAP2-AS1 in 78 breast cancer samples and their paired adjacent non-cancerous tissues (ANCTs) by means of real time PCR. All mentioned genes were significantly down-regulated in tumoral tissues compared with ANCTs (P values less than 0.000). Relative expression of VIM-AS1 in tumoral tissues versus ANCTs was associated with menopause age (P = .02) in a way that this gene was down-regulated in most of patients whose menopause age was between 40 and 50 years. Moreover, AGAP2–AS1 relative expression was associated with patients' body mass index (P = .03). There were trends toward association between VIM relative expression and tumor size (P = .07) and association between VIM-AS1 relative expression and obesity (P = .06). Expression of VIM was significantly higher in tumoral tissues of patients who had history of hormone replacement therapy compared with those without such history (P = .03). Moreover, expression levels of both VIM and AGAP2-AS1 were lower in patients whose menarche age was between 10 and 12 years old compared with those whose menarche age was between 13 and 15 years old (P values = .01 and 0.04, respectively). Transcript quantities of VIM, VIM-AS1, AGAP2 and AGAP2-AS1 were correlated with each other both in tumoral tissues and in ANCTs. Among four assessed genes, AGAP2 had the best diagnostic power for discrimination of tumoral tissues from ANCTs (AUC value = 0.87). Combination of four genes led to enhancement of AUC value to 0.94. The current study shows the importance of VIM and its associated lncRNAs in breast cancer and potentiates these genes as biomarkers for this malignancy. Moreover, these lncRNAs might be regarded as therapeutic targets in breast cancer.

Suicidal behavior as a psychological problem with high public health burden is associated with a number of genetically determined risk factors. In the current study, we investigated the association between two polymorphisms within the NINJ2 gene and risk of suicide in an Iranian population. The study included 295 individuals who attempted suicide with soft suicide methods, 234 suicide victims and 410 normal controls. The rs11833579 SNP was associated with death from suicide in a codominant model in that the AG genotype decreased the risk of death from suicide compared with the GG genotype (OR (95% CI) = 0.49 (0.34-0.71), adjusted P value = 4e-04). This SNP was also associated with death from suicide in dominant (AG + AA versus GG: OR (95% CI) = 0.63 (0.46-0.87), adjusted P value = 0.011) and overdominant (AG versus GG + AA: OR (95% CI) = 0.49 (0.35-0.69), adjusted P value 0.0001) models. In addition, this SNP was associated with soft suicide attempts in a codominant model (AG versus AA + GG: OR (95% CI) = 0.7 (0.5-0.98), adjusted P value = 0.02). The rs3806263 SNP was associated with death from suicide in allelic (A versus G: OR (95% CI) = 1.48 (1.17-1.88), adjusted P value = 0.002), codominant (AA versus GG: OR (95% CI) = 3.14 (1.89-5.21), adjusted P value 0.0001), recessive (AA versus GG + AG: OR (95% CI) = 3.47 (2.15-5.61), adjusted P value 0.0001), overdominant (AG versus AA + GG: OR (95% CI) = 0.62 (0.45-0.87), adjusted P value = 0.0092) and log-additive models (OR (95% CI) = 1.45 (1.15-1.83), adjusted P value = 0.0034). When comparing allele/genotype frequencies of this SNP between suicide victims and soft suicide attempters, significant associations were found in allelic, codominant, recessive and log-additive models. The AG haplotype (rs11833579 and rs3806263, respectively) was significantly less prevalent among suicide victims compared with controls (OR (95% CI) = 0.37 (0.26-0.52), adjusted P value 0.0001). This haplotype was also less prevalent among suicide victims vs. soft suicide attempters (OR (95% CI) = 0.43 (0.31-0.61), adjusted P value 0.0001). The GA haplotype (rs11833579 and rs3806263, respectively) was less frequent among suicide victims compared with controls (OR (95% CI) = 0.63 (0.45-0.89), adjusted P value = 0.0156). Finally, the AA haplotype was more prevalent among suicide victims compared with both controls (OR (95% CI) = 2.37 (1.56-3.6), adjusted P value = 0.0002) and soft suicide attempters (OR (95% CI) = 1.92 (1.32-2.78), adjusted P value = 0.0012). Thus, these two SNPs might be regarded as genetic determinants of suicide risk in Iranian populations. Further studies in different populations are needed to verify these results.

Long non-coding RNAs (lncRNAs) have been vastly investigated for their critical roles in the pathogenesis of breast cancer. Yet, the expression pattern and clinical significance of three lncRNAs namely CTBP1AS2, LINC-ROR and SPRY4-IT1 in breast cancer are not completely clarified. In the present investigation, we assessed expression of these lncRNAs in breast cancer tissues and paired non-cancerous specimens from the same patients using quantitative real time PCR. Notably, expression of CTBP1AS2, LINC-ROR and SPRY4-IT1 were upregulated in breast cancer tissues compared with non-cancerous tissues (ER = 17.62, P value0.000; ER = 4.62, P value = 0.001 and ER = 3.47, P value = 0.005, respectively). Relative expression of LINC-ROR in tumoral tissues compared with non-tumoral tissues was associated with a history of hormone replacement therapy (P = 0.04). Expression levels of CTBP1AS2, LINC-ROR and SPRY4-IT1 were significantly correlated with each other in both tumoral and non-tumoral tissues. The strongest correlations were detected between CTBP1AS2/ LINC-ROR and CTBP1AS2/ SPRY4-IT1 pairs in non-tumoral tissues. CTBP1AS2 and SPRY4-IT1 had the best sensitivity (80%) and specificity (64%) values, respectively. Based on AUC values, the best diagnostic power belonged to CTBP1AS2. The current study potentiates CTBP1AS2, LINC-ROR and SPRY4-IT1 as putative contributors in the pathogenesis of breast cancer and suggests these lncRNAs as candidates for functional analysis in this kind of cancer.

The nuclear factor-κB (NF-κB) has a pivotal role in the pathogenesis of several cancers including gastric cancer. We have recently reported dysregulation of a number of NF-κB-associated lncRNAs in a variety of human disorders including breast cancer and coronary artery disease. In the current study, we evaluated expression of five NF-κB-associated lncRNAs (CHAST, ADINR, DICER1-AS1, HNF1A-AS1 and NKILA) and two NF-κB-associated-mRNA coding genes (CEBPA and ATG5) in gastric cancer tissues and their paired non-cancerous tissues using real time PCR method. Expression of DICER-AS1 was significantly down-regulated in gastric cancer tissues compared with the corresponding non-cancerous tissues (Expression ratio = 0.23, P value = .01). Expressions of other genes were not significantly different between these two sets of samples. Relative expression of DICER1-AS1 in cancer tissues versus non-cancerous tissues tended to associated with histological grade (P = .05). Tumoral expression levels of NKILA, ADINR, CEBPA and HNF1A-AS1 were significantly higher in patients with positive family history of cancer compared with those without such history (P values = .03, 0.02, 0.02 1nd 0.03, respectively). Besides, expression levels of NKILA, ADINR, DICER1-AS1, CEBPA, CHAST, HNF1A-AS1 and ATG5 were lower in H. pylori-infected tissues (P values = .01, 0.02, 0.03, 0.01, 0.004, 0.004 and 0.04, respectively). The lowest tumoral expression of DICER1-AS1 was detected in stage II cancers, while the highest expression of this lncRNA was reported in a single stage I tumor tissue. Similar pattern of expression was detected for ATG5. Significant pairwise correlations were demonstrated between expression levels of NF-ƙB-associated genes in both gastric cancer tissues and non-cancerous tissues. Expression levels of DICER1-AS1 had sensitivity and specificity values of 63.3% and 63.3% in differentiating between tumoral and non-tumoral tissues (Estimate criterion>6.96, J = 0.27, P value = .01, AUC = 0.67). Although previous studies have reported involvement of NF-κB pathway in the pathogenesis of gastric cancer, among the reported lncRNAs associated with this pathway, we could only detect differential expression of DICER1-AS1 between tumoral and non-tumoral tissues. Thus, the mechanism underlying dysregulation of this pathway might be different among various cancers.

Aim: Cancer-testis antigens (CTAs) have specific expression in gametogenic tissues and aberrant expression in cancers. Materials & methods: We assessed expression of five testis-specific genes namely KIF2B, CST8, TMEM225, RBM46, OAZ3 in bladder cancer tissues, adjacent non-neoplastic tissues and urinary cell pellets (UCPs) of bladder cancer patients compared with nonmalignant conditions.Results: Expressions of all CTAs were higher in UCPs of bladder cancer patients compared with nonmalignant conditions. RBM46 expression in UCPs was higher in patients with recurrent tumors compared with primary tumors and in patients without hematuria compared with those having hematuria. TMEM225 expression in tumoral tissues was higher in high-grade tumors compared with low-grade tumors. Conclusion: Expression analysis of CTAs in UCP might provide diagnostic information about bladder cancer.

Fatemeh Yazarlou,1 Mohammad Hossein Modarressi,1 Seyed Javad Mowla,2 Vahid Kholghi Oskooei,3 Elahe Motevaseli,4 Leila Farhady Tooli,5 Leila Nekoohesh,6 Maryam Eghbali,1 Soudeh Ghafouri-Fard,3 Mandana Afsharpad7 1Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Faculty of Biological Sciences, Department of Genetics, Tarbiat Modares University, Tehran, Iran; 3Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Microbiology, School of Biology, College of Science, Tehran University, Tehran, Iran; 6Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 7Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences, Tehran, Iran Background: Long non-coding RNAs (lncRNAs) and exosomes have been regarded as components of cell signal transmission that modulate indigenous cellular microenvironments. Exosomes also participate in relocation of functional lncRNAs between cells. Methods: In the present study, we evaluated expression of LINC00355, LINC00958, UCA1-201, UCA1-203, and MALAT1 lncRNAs in urinary exosomes isolated from transitional cell carcinoma (TCC) of bladder, non-malignant urinary disorders, and normal subjects. Results: LINC00355, UCA1-203, and MALAT1 expression was significantly higher in TCC patients compared to controls (non-malignant or normal samples). However, UCA1-201 expression was significantly decreased in TCC patients compared with controls. LINC00355 and MALAT1 expression was significantly lower in cigarette smokers and opium-addicted TCC patients, respectively. On the other hand, LINC00355 expression tended to be higher in opium-addicted TCC patients. The proposed panel of lncRNAs (composed of UCA1-201, UCA1-203, MALAT1, and LINC00355) had 92% sensitivity and 91.7% specificity for diagnosis of bladder cancer from normal samples. Conclusion: Transcript levels of lncRNAs in urinary exosomes are potential diagnostic biomarkers in bladder cancer. Keywords: lncRNA, exosome, bladder cancer

Long non-coding RNAs (lncRNAs) have been shown to participate in the pathogenesis of a variety of cancers including breast cancer. The lncRNA Carbonyl reductase 3-Antisense 1 (CBR3-AS1) has been implicated in some human malignancies in association with androgen receptor (AR). In the present study, we evaluated the expression of CBR3-AS1 and AR transcripts in 52 breast cancer tissues, their corresponding adjacent non-cancerous tissues (ANCTs) and two breast cancer cell lines (MDA-MB-231 and MCF-7). We extracted data of our previously published work regarding expression level of Zinc-finger enhancer binding protein (ZEB1) in the same cohort of patients. CBR3-AS1 was up-regulated in MDA-MB-231 compared with ANCTs. AR was significantly down-regulated in both breast cancer cell lines compared with ANCTs. AR expression was lower in tumoral tissues compared with ANCTs but it did not reach the level of significance. CBR3-AS1 expression has been shown to be significantly elevated in tumor tissues compared with ANCTs (fold change = 4.178, P = 0.021). No significant associations have been detected between the level of transcripts and patients' data except for an association between AR expression and cancer stage (P = 0.037). In luminal B subtype, AR transcript levels were more frequently down-regulated (P = 0.015). A significant correlation has been detected between the levels of CBR3-AS1 and AR transcripts in tumor tissues but not in ANCTs. No significant correlation has been detected between the levels of AR and ZEB1 transcripts in tumor tissues or in ANCTs. The observed significant up-regulation of CBR3-AS1 in breast cancer tissues and cell lines is in line with the suggested oncogenic role of this lncRNA in other cancers.

Background Long non-coding RNAs (lncRNAs) have several important functions in the regulation of cell homeostasis and cell fate. Consequently, abnormal transcription of lncRNAs has been correlated with malignant transformation of cells. These human transcripts have been shown to participate in the progression of gastric cancer. Methods In the current project, we evaluated expression of a panel of lncRNAs including HULC, MALAT1, FAS-AS1, GAS5, PVT1, OIP5-AS1 and THRIL in 30 gastric cancer tissues and paired adjacent non-cancerous tissues (ANCTs) using quantitative real-time PCR. Results HULC, OIP5-AS1 and THRIL transcription quantities were significantly lower in gastric tumors compared to ANCTs (P values = .02, 0.02 and 0.007, respectively). Relative transcription quantities of HULC, MALAT1, OIP5-AS1, PVT1, FAS-AS1 and THRIL were associated with the site of the primary tumor (P values = .002, 0.003, 0.002, 0.002, 0.002, and 0.001, respectively). Moreover, relative expression levels of PVT1 were associated with history of smoking (P value = .04). Correlations were identified between transcript quantities of these lncRNAs in both tumor samples and ANCTs. Receiver operating characteristic curve assessment demonstrated that THRIL had the highest diagnostic power among the mentioned lncRNAs (area under curve (AUC) = 0.72, P value = .001). HULC and OIP5-AS1 ranked afterwards (AUC values of 0.69 and 0.68; P values = .005 and 0.007, respectively). Conclusion The current investigation underscores the dysregulation of these transcripts in gastric cancer specimens and suggests a number of these transcripts for further assessments of their suitability as cancer biomarkers.

Salivary gland tumors are complex neoplastic disorders with unidentified basis. Based on the importance of vitamin D receptor signaling in the pathogenesis of neoplastic conditions, we measured expression of some mRNA coding genes (VDR, CYP24A1 and CYP25B1) and long non-coding RNAs (SNHG16, SNHG6, LINC00346 and LINC00511) from this pathway in 42 paraffin-embedded blocks from 37 patients with different disorders originated from salivary gland. Total RNA was extracted from these samples using commercial kits and expression of mentioned genes was measured in these samples using quantitative real time PCR method. Expression of LINC00511 was lower in tumor samples compared with pleomorphic adenoma (PA) samples (Expression ratio (ER) = 0.08, P value = 0.009). Yet, its expression was higher in PA samples compared with non-cancerous tissues adjacent to carcinoma samples (ER = 21.77, P = 0.009). In addition, its expression was lower in both adenoid cystic carcinoma and mucoepidermoid carcinoma samples compared with PA samples (ER = 0.11, P value = 0.046 and ER = 0.07, P value = 0.017, respectively). Expression of other genes was statistically similar between different lesions. Therefore, LINC00511 might be used as a marker for separation of salivary gland carcinomas from PA samples.

Psoriasis is a complex disorder with genetic background. Previous studies have reported the presence of some genetically-influenced factors for this disorder. In the current study, we genotyped rs2067079 and rs6790 polymorphisms of GAS5 lncRNA in Iranian patients with psoriasis and healthy controls. Genotype frequencies of rs2067079 and rs6790 were in accordance with the Hardy-Weinberg equilibrium both in cases and controls. Distributions of alleles/genotypes of rs2067079 and rs6790 polymorphisms were similar between patients with psoriasis and healthy controls. None of these SNPS were associated with risk of psoriasis in any inheritance model. We also appraised association between GAS5 haplotypes and risk of psoriasis. Frequencies of CG, TG, CA and TA haplotypes (rs2067079 and rs6790) were statistically similar between patients with psoriasis and healthy controls. Thus, mentioned polymorphisms are not associated with risk of psoriasis in Iranian population.

Long non-coding RNAs affect cancer progression and gastric cancer(GC) tumorigenesis impressively. We investigated the expression of a novel long intergenic non-coding RNA—lincRNA-AC064834.1(ENST00000413290.1)—in GC patients. LincRNA-AC064834.1 was selected from the differentially expressed lncRNA transcripts by RNA-seq results. Quantitative RT-PCR examined the lincRNA-AC064834.1 expression in GC tissues and adjacent noncancerous tissues(ANCTs) (n = 80 samples). The association between the expression level of AC064834.1 and clinicopathology was tested. In addition, the suitability of the transcript level of this gene in differentiation of tumoral from non-tumoral tissues was assessed by plotting the ROC curve. The results showed that the AC064834.1 relative expression levels were considerably higher in tumor tissues than in ANCTs (Fold change/log2 standard error, 4.52 (0.22–73.77); p = 0.006). The overall sensitivity and specificity of AC064834.1 in GC diagnosis were 67.5%. RNA expression level of AC064834.1 did not significantly correlate with clinicopathologic characteristics. The lincRNA-AC064834.1 might serve as a novel potential biomarker for GC.

Aim: To evaluate the expression of the growth arrest-specific 8 (GAS8) and its antisense (GAS8-AS1) in gastric cancer. Background: GAS8 exists in a genomic region that is recurrently deleted in breast and prostate cancer. This gene contains a long non-coding RNA, namely GAS8-AS1 whose roles in the regulation of GAS8 has been reported in hepatocytes. GAS8-AS1 has also been regarded as a putative tumor suppressor gene in papillary thyroid cancer and hepatocellular carcinoma. Methods: In the present study, we evaluated expression levels of GAS8 and GAS8-AS1 in 30 gastric cancer tissues and their corresponding adjacent non-cancerous tissues (ANCTs). Results: GAS8 was significantly down-regulated in tumor tissues compared to ANCTs (Expression ratio=0.29, p

Schizophrenia as a common disabling psychiatric disorder has been associated with dysregulation of several genes and pathways among them are those being regulated by long non-coding RNAs (lncRNAs). Based on the acknowledged roles of lncRNAs in neurodevelopment, in the current study, we assessed expression of six lncRNAs namely HOXA-AS2, Linc-ROR, MALAT1, MEG3, SPRY4-IT1 and UCA1 in peripheral blood of 60 patients with schizophrenia and 60 healthy subjects. HOXA-AS2, Linc-ROR, MEG3, SPRY4-IT1 and UCA1 levels were significantly higher in total patients compared with total controls. However, when evaluating expression of genes in sex-based subgroups, the differences in the expression of these lncRNAs were significant only among females. Assessment of partial correlation between expression of lncRNAs and age of study participants after controlling the effect of sex, revealed significant correlations for HOXA-AS2, MALAT1 and UCA1 in both patients and controls. Besides, expressions of Linc-ROR and SPRY4-IT1 were correlated with age only in patients. Significant pairwise correlations were recognized between expression levels of lncRNAs in both patients with schizophrenia and controls. Based on the area under curve (AUC) values, SPRY4-IT1 had the best performance in differentiation of female patients with schizophrenia from female controls (AUC = 0.85, P Linc-ROR, MEG3, SPRY4-IT1 and UCA1 expression levels could differentiate female patients with 95.2% sensitivity, 76.9% specificity and diagnostic power of 0.88 (P

AIM Nicotinamide Nucleotide Transhydrogenase (NNT) gene encodes a protein, which is an important antioxidative enzyme that converts NADH to NADPH. This enzyme provides a significant proportion of the entire NADPH resource in the mitochondria. Previous reports have shown possible contribution of this gene in the carcinogenesis process. METHODS In the current research, we evaluated expression levels of NNT gene and a naturally occurring antisense RNA (NNT-AS1) in gastric cancer specimens compared to their corresponding adjacent noncancerous tissues (ANCTs). RESULTS Both NNT1 and NNT-AS1 genes were significantly downregulated in tumor tissues compared to ANCTs (expression ratio = 0.369, p = .045 and expression ratio = 0.368, p = .043, respectively). Transcript levels of NNT1 and NNT-AS1 were associated with the location of the primary tumor (p = .003 and .002, respectively). Moreover, expressions of both genes were significantly elevated in tumors with lymphatic/vascular invasion compared to tumors without lymphatic/vascular invasion (p = .001 and p = .005). No other remarkable associations were noticed between transcript levels of genes in tumor tissues and patients' information. Based on the area under curve (AUC) values in the receiver operating characteristic (ROC) curves, the diagnostic power of NNT1 and NNT-AS1 were estimated to be 0.62 and 0.63, respectively. CONCLUSIONS Although we demonstrated dysregulation of NNT1 and NNT-AS1 in gastric tumor specimens in association with clinical data of patients, these two genes are not supposed to be appropriate biomarkers for gastric cancer.

Shugoshin-like protein 1 (SGO1) participated in the proper progression of mitosis. This fundamental role has indicated the importance of this gene in the pathogenesis of cancer as a disorder of mitotic cell division. A previous high throughput study of long non-coding RNAs (lncRNAs) expression in lung cancer has identified aberrant expression of SGO1-antisense 1 (SGO1-AS1) in these specimens. In the current study, we quantified expression of SGO1 and SGO1-AS1 in 39 breast cancer tissues and their paired adjacent non-cancerous tissues (ANCTs). Expression of SGO1-AS1 was considerably decreased in tumoral tissues compared with ANCTs (expression ratio = 0.49, P value = 0.03). However, we could not identify significant difference in expression of SGO1 between these two sets of specimens (expression ratio = 2.9, P value = 0.2). Transcript quantities of SGO1-AS1 were associated with age at disease onset (P= 0.01). Expression of either gene was associated with hormone receptors status or clinical features such as grade and stage. There was an inverse correlation between expressions of genes in both sets of samples. Finally, transcript amounts of SGO1-AS1 could distinguish these two sets of samples with accuracy of 63% (P value = 0.03). Our results imply significance of SGO1-AS1 in breast cancer and necessitate conduction of mechanistic studies to find the molecular pathways in this regard.