Down-regulation of LINC-ROR, HOXA-AS2 and MEG3 in gastric cancer.

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 LINC-ROR, HOXA-AS2, MEG3 and HOTTIP lncRNAs in gastric cancer samples and nearby non-cancerous samples. Expression levels of LINC-ROR, HOXA-AS2 and MEG3 lncRNAs have been lower in gastric cancer samples compared with nearby non-cancerous samples (Expression ratios = 0.26, 0.37 and 0.36; P values = 0.021, 0.015 and 0.032, respectively). However, expression levels of HOTTIP were not significantly different between gastric cancer tissues and nearby tissues (P value = 0.43). HOTTIP expression was associated with tumor size (P value = 0.04). In addition, MEG3 expression was associated with site of primary tumor (P = 0.0003). Expressions of LINC-ROR and HOXA-AS2 were not associated with any clinical or pathological parameter. ROC curve analysis revealed that HOXA-AS2 and LINC-ROR could significantly differentiate between gastric cancer samples and nearby non-cancerous tissues (AUC values = 0.68 and 0.64; P values = 0.01 and 0.04, respectively). Taken together, the current investigation provides clues for contribution of LINC-ROR, HOXA-AS2 and MEG3 lncRNAs in gastric carcinogenesis and warrants further mechanistical assays.

Association analysis of MALAT1 polymorphisms and risk of psoriasis among Iranian patients.

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.

Investigation of FADS Gene Cluster Single Nucleotide Polymorphisms in End-Stage Renal Disease Compared With Normal Controls.

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.

SNP-SNP interactions of oncogenic long non-coding RNAs HOTAIR and HOTTIP on gastric cancer susceptibility.

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.

Expression profiling revealed up-regulation of three lncRNAs in breast cancer samples.

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 value<0.000; 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.

DICER-AS1 lncRNA: A putative culprit in the pathogenesis of gastric 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.

In silico identification of MAPK14-related lncRNAs and assessment of their expression in breast cancer samples.

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.

Expression analysis of vimentin and the related lncRNA network in breast cancer.

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.

Expression analysis of growth arrest specific 8 and its anti-sense in breast cancer tissues.

The Growth arrest specific 8 (GAS8) and its anti-sense transcript (GAS8-AS1) are located in a genomic region that is frequently mutated in breast cancer. These transcripts have established tumor suppressor effects in some human malignancies. In the current investigation, we aimed at identification of the role of GAS8 and GAS8-AS1 in breast cancer. We measured gene expression of GAS8 and GAS8-AS1 in paired tumoral and non-tumoral tissues obtained from 88 breast cancer patients by means of real time PCR. No significant differences were identified in expressions of GAS8 and GAS8-AS1 in tumoral samples compared with non-tumoral tissues (Fold changes = 1.53 and 1.71; P values = .28 and 0.14 respectively). Transcript levels of GAS8-AS1 was significantly correlated with estrogen receptor (ER) status (P = .01). Expression of GAS8 gene was associated with history of oral contraceptive use (P = .04). The similar expressions of GAS8 and GAS8-AS1 genes in tumoral and non-tumoral tissues of breast in spite of previous reports regarding their fundamental tumor suppressor roles in other tissues show that these genes are not involved in the pathogenesis of breast cancer. So, these genes have distinct roles in diverse tissues.

Gene expression of indoleamine and tryptophan dioxygenases and three long non-coding RNAs in breast cancer.

The kynurenine pathway (KP) has a principal role in the metabolism of tryptophan. This pathway is also involved in the pathogenesis of cancer. We evaluated expression of two rate limiting enzymes from this pathway (IDO1 and TDO2) as well as three long non-coding RNAs (lncRNAs) that have been predicted to alter expression of IDO1 (ITGB2-AS1, HCP5 and MIR155HG) in 82 breast cancer tissues and their adjacent non-cancerous tissues (ANCTs). While IDO1 expression levels were not significantly different between malignant tissues and ANCTs (expression ratio = 0.56, P = .21), TDO2 was significantly down-regulated in malignant tissues compared with ANCTs (Expression ratio = 0.001, P < .001). Among lncRNAs, expression of HCP5 was significantly lower in malignant tissues compared with ANCTs (Expression ratio = 0.17, P < .001). However, expression of ITGB2-AS1 was higher in malignant tissues compared with ANCTs (Expression ratio = 3.38, P = .01). Expressions of genes were not associated with any of clinical or demographic data of patients. However, there were trends towards association between IDO1 expression and tumor size as well as estrogen receptor (ER) status (P values 0.09 and 0.08 respectively). Significant pairwise correlations were found between expression levels of genes especially in ANCTs. Notably, TDO2 expression levels were correlated with expression of all other genes in ANCTs but none of them in tumor tissues. Based on the area under curve (AUC) values, HCP5 and TDO2 had "fair" diagnostic power (AUC values of 0.73 and 0.72). Notably, combination of HCP5, ITGB2-AS1 and TDO2 genes increased the diagnostic power to the level of "good". The current investigation underscores the role of KP in breast cancer and potentiates some genes within this pathway as diagnostic markers in breast cancer.

SE translocation gene but not zinc finger or X-linked factor is down-regulated in gastric cancer.

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<0.05) and in ANCTs (R2=0.23, P<0.05). CONCLUSION: Overall, our results imply the role of SET1 in gastric cancer and potentially functional associations between this gene and ZFX in gastric tissues.

Expression analysis of CD24 and CD44 transcripts in Iranian breast cancer patients.

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.

Sexual dimorphism in up-regulation of suppressors of cytokine signaling genes in patients with bipolar disorder.

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.

GAS8 and GAS8-AS1 expression in gastric cancer.

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<0.001). Although the expression of GAS8-AS1 was higher in tumor tissues compared to ANCTs (Expression ratio=2.15), it did not reach the level of significance (p=0.12). GAS8 expression was associated with the site of the primary tumor (p=0.01). GAS8-AS1 expression was significantly higher in tumors with lymphatic/ vascular invasion compared with those without lymphatic/ vascular invasion (p=0.03). Significant pairwise correlations were detected between expression levels of GAS8 and GAS8-AS1 in tumor tissues and ANCTs. Based on the results of the ROC curve, the diagnostic power of transcript levels of GAS8 in gastric tissues was estimated to be 76%. CONCLUSION: The current study underscores the roles of GAS8 and GAS8-AS1 in gastric carcinogenesis and warrants future functional studies to unravel the underlying mechanism of such contribution.

Downregulation of nicotinamide nucleotide transhydrogenase and its naturally occurring antisense RNA in gastric cancer.

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.

Brain-derived neurotrophic factor downregulation in gastric cancer.

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 = <.001). We also found higher amounts of both genes in malignant samples obtained from older patients (P = .01 and P = .03 for BDNF and BDNF-AS, respectively). Besides, BDNF expression was higher in tumors with lymphatic/vascular invasion (P = .01). There was also a trend toward upregulation of BDNF-AS in tumors with lymphatic/vascular invasion (P = .05). The current study underscores the role of BDNF and BDNF-AS in the pathogenic process leading to gastric cancer.

Transcription Levels of nicotinamide nucleotide transhydrogenase and Its Antisense in Breast Cancer Samples.

OBJECTIVE: To evaluate association of patients' clinicopathological data with expression of nicotinamide nucleotide transhydrogenase (NNT) and naturally occurring antisense RNA of the same gene locus (NNT-AS1) in breast cancer samples. MATERIALS AND METHODS: In the current case-control study, mean expressions of NNT and NNT-AS1 were assessed in 108 breast tissue samples including 54 invasive ductal carcinoma samples and 54 adjacent non-cancerous tissues (ANCTs) by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: NNT expression was not significantly different between tumor tissues and ANCTs. However, NNT-AS1 expression was significantly down-regulated in tumor tissues compared to ANCTs (expression ratio=0.51, P=0.01). NNT-AS1 expression was significantly higher in estrogen receptor (ER) negative samples, in comparison with ER positives (P=0.01). No considerable difference was found in the gene expressions between other subcategories of patients. Considerable correlations were detected between expression levels of these two genetic loci in both tumor tissues and ANCTs. CONCLUSION: In the current study, for the first time we simultaneously assessed expression of NNT and NNT-AS1 in breast cancer tissues. This study highlights association of ER status with dysregulation of NNT-AS1 in breast cancer tissues. Future researches are necessary to explore the function of this long non-coding RNA (lncRNA) in the pathogenesis of breast cancer.

Assessment of the expression pattern of mTOR-associated lncRNAs and their genomic variants in the patients with breast cancer.

The mechanistic target of rapamycin (mTOR) is a fundamental component of a signaling pathway that is involved in the pathogenesis of breast cancer via different mechanisms. This pathway is functionally linked with a number of small nucleolar RNA host genes (SNHGs). In the present project, we have searched for the expression quantitative trait loci (eQTLs) within SNHGs that are possibly involved in the pathogenesis of breast cancer. Following this in silico step, we have assessed expression levels of mTOR and four SNHGs in malignant and nonmalignant samples obtained from 80 patients with breast cancer. We also genotyped rs4615861 of SNHG3 and rs3087978 of SNHG5 in the peripheral blood of patients. SNHG12 expression was not detected in any of the assessed malignant or nonmalignant tissues. So this gene was excluded from further steps. Expression of mTOR and other three long noncoding RNAs (lncRNAs) were significantly increased in the malignant tissues compared with the nonmalignant tissues. When classifying patients into down-/upregulation categorized based on the transcript levels of each gene in malignant tissue versus nonmalignant tissues, we noticed associations between expression of SNHG1 and stage (p = 0.03), expression of SNHG5 and grade (p = 0.05), as well as between expression of SNHG3 and history of oral contraceptive use (p = 0.04). We also detected higher levels of SNHG3 expression in estrogen receptor/progesterone receptor (ER/PR) negative tumors compared with the ER/PR positive tumors (p = 0.003 and p = 0.01, respectively). Moreover, there was a trend toward higher expression of this lncRNA in HER2-positive tumors compared with the HER2-negative ones (p = 0.07). Combination of transcript levels of all genes could differentiate malignant tissues from nonmalignant tissues with the diagnostic power of 69% (p = 0.0001). The rs3087978 was associated with the expression of mTOR in malignant tissues in a way that TT and TG genotypes were associated with the higher and lower levels of expressions, respectively (p = 0.01). The current study underscores the significance of SNHGs in the pathogenesis of breast cancer.

Sex-based dimorphisms in expression of BDNF and BACE1 in bipolar patients.

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 ±â€¯standard deviation (SD) = 36.5 ±â€¯9.32) and 50 healthy subjects (mean age ±â€¯SD = 33.62 ±â€¯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.

Expression of long noncoding RNAs in breast cancer in relation to reproductive factors and tumor characteristics.

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.