Identification of miR-125a and miR-106b signature as a potential diagnostic biomarker in breast cancer tissues.

MicroRNAs (miRNAs) have essential roles in the etiology of breast cancer and are regarded as possible markers in this malignancy. In order to find new markers for breast cancer, the current study has measured expression level of four miRNAs, namely miR-125a, miR-106b, miR-96 and miR-92a-3p in the paired breast samples. Expression levels of miR-125a and miR-106b were higher in tumoral tissues compared with control tissues (Expression ratios (95% CI) = 4.01 (1.96-8.19) and 3.9 (1.95-7.81); P values = 0.0005 and 0.0003, respectively). miR-106b and miR-125a differentiated between malignant and non-malignant tissues with AUC values of 0.7 and 0.67, respectively. We detected association between expression of miR-106b and clinical stage (P = 0.03), in a way that its expression was the lowest in the advanced stages. Finally, significant relationships were found between miR-96 and miR-125a in both tumoral and non-tumoral specimens (ρ = 0.76 and 0.69, respectively). This nonparametric measure of rank correlation also showed relationship between miR-106b and miR-96 in both sets of samples (ρ = 0.63 and 0.61, respectively). Cumulatively, the assessed miRNAs, particularly miR-125a and miR-106b are putative targets for further expression and functional assays in breast cancer.

Association Between RORA Polymorphisms and Obesity.

RORα is a transcription factor encoded by RORA gene. This protein is involved in several metabolic conditions, including obesity. We assessed association between two polymorphisms within this gene (namely rs11639084 and rs4774388) and severe obesity in Iranian population. Both SNPs were associated with obesity in all models (P < 0.0001) except for over-dominant model. T allele of rs11639084 was associated with this trait with OR (95% CI) of 16.85 (13.11-21.67) and was considered as the risk allele. Allelic model best fit the data, since the AIC value for this model was the highest (AIC = 28.82). In the co-dominant model, TT genotype was associated with obesity with OR (95% CI) of 301.6 (137.4-662.1). This genotype was shown to be the risk genotype in the recessive model when compared with TC+CC (OR (95% CI) = 60.54 (30.35-120.7)). The C allele of rs4774388 was shown to be the risk allele with OR (95% CI) of 4.61 (3.72-5.71). In the recessive model, the CC genotype was associated with the mentioned trait with OR (95% CI) of 9.92 (6.62-14.8). This model best fit the data (AIC = 37.08). Cumulatively, the current study suggests contribution of RORα to the pathogenesis of obesity.

Alteration in the expression of long non-coding RNAs in the circulation of migraineurs.

BACKGROUND: Current studies have shown emerging roles of lncRNAs in the pathobiology of neuropathic pain and migraine. METHODS: We have chosen five lncRNAs, namely, PVT1, DSCAM-AS, MEG3, LINC-ROR, and SPRY4-IT1 for assessment of their expression in the circulation of migraineurs. RESULTS: Expressions of PVT1 and MEG3 were higher in total migraineurs and both subgroups compared with controls (P < 0.0001). Meanwhile, expression of both lncRNA was higher in migraineurs with aura versus migraineurs without aura (P value < 0.0001 and = 0.01, respectively). Expression of DSCAM-AS1 was not different between any groups of patients compared with controls. Expression of LINC-ROR was elevated in total patients and patients with aura compared with controls (P value = 0.0002 and < 0.0001, respectively). It was also over-expressed in migraineurs with aura vs. migraineurs without aura (P = 0.01). Finally, expression of SPRY4-IT1 was higher in total patients and patients without aura compared with migraine-free persons (P values < 0.0001). Expressions of five mentioned lncRNAs were correlated in almost all study groups. In patients without aura, correlations were significant only for two pairs (SPRY4-IT1/PVT1 and SPRY4-IT1/DSCAM-AS1). PVT1 and MEG3 had the appropriate AUC, sensitivity and specificity values for separation of total migraineurs and both groups of patients from controls. The highest AUC value was reported for PVT1 in separation of migraineurs with aura from healthy controls (AUC = 0.98). CONCLUSION: Cumulatively, our study shows evidence for deregulation of lncRNAs in migraineurs.

The association of infant and mother gut microbiomes with development of allergic diseases in children: a systematic review.

OBJECTIVE: It is believed that gut microbiota alteration leads to both intestinal and non-intestinal diseases in children. Since infants inherit maternal microbiota during pregnancy and lactation, recent studies suggest that changes in maternal microbiota can cause immune disorders as well. This systematic review was designed to assess the association between the child and mother's gut microbiome and allergy development in childhood. DATA SOURCES: In this systematic review, international databases including PubMed, Scopus, and ISI/WOS were searched until January 2023 to identify relevant studies. STUDY SELECTIONS: Observational studies that analyzed infant or maternal stool microbiome and their association with allergy development in children were included in this study. Data extraction and quality assessment of the included studies were independently conducted by two researchers. RESULTS: Of the 1694 papers evaluated, 21 studies examined neonate gut microbiome by analyzing stool samples and six studies examined maternal gut microbiota. A total of 5319 participants were included in this study. Asthma followed by eczema and dermatitis were the most common allergy disorders among children. Urbanization caused a lack of diversity in the bacterial microbiota as well as lower levels of Bifidobacterium and Lachnospira associated with a higher risk of allergy. In contrast, higher levels of Roseburia and Flavonifractor were associated with lower allergy risk. CONCLUSIONS: This systematic review shows that gut microbiota may be associated with allergy development. Further studies are required to provide a definitive answer.

Integrated bioinformatics approaches and expression assays identified new markers in pituitary adenomas.

Pituitary adenomas (PA) include about one third of primary central nervous tumors in adolescent and young adult. Despite extensive research, the underlying mechanism of PA tumorigenesis is still unknown. In the present study, through bioinformatics analysis of a PA-related dataset downloaded from GEO database, we attempted to identify pair(s) of lncRNA/target mRNA whose expression changes may be involved in the tumorigenesis of PAs. For this end, we evaluated expression of a set of bioinformatically obtained genes in 46 PA tissues against adjacent non-tumor pituitary tissues. The bioinformatics step led to selection of four genes for validation through expression assays. Expression levels of HIF1A and MAPK1 were increased in NFPA tissues (P < 0.0001 and =0.0042, respectively). Expression level of BANCR was significantly decreased in tumor tissues (P < 0.0001). However, expression of STAT3 was not meaningfully different between the two tissue types (P = 0.56). Since there was no significant correlation between MAPK1 and BANCR expressions in either tumor or adjacent normal tissues, the regulatory effect of BANCR on MAPK1 was not confirmed. In conclusion, this study offers information about deregulation of bioinformatically identified genes in PA tumors and indicates that further studies in this field is needed to understand the involved molecular mechanisms.

Expression assay of calcium signaling related lncRNAs in autism.

BACKGROUND: Calcium signaling has essential roles in the neurodevelopmental processes and pathophysiology of related disorders for instance autism spectrum disorder (ASD). METHODS AND RESULTS: We compared expression of SLC1A1, SLC25A12, RYR2 and ATP2B2, as well as related long non-coding RNAs, namely LINC01231, lnc-SLC25A12, lnc-MTR-1 and LINC00606 in the peripheral blood of patients with ASD with healthy children. Expression of SLC1A1 was lower in ASD samples compared with control samples (Expression ratio (95% CI) 0.24 (0.08-0.77), adjusted P value = 0.01). Contrary, expression of LINC01231 was higher in cases compared with control samples (Expression ratio (95% CI) 25.52 (4.19-154), adjusted P value = 0.0006) and in male cases compared with healthy males (Expression ratio (95% CI) 28.24 (1.91-418), adjusted P value = 0.0009). RYR2 was significantly over-expressed in ASD children compared with control samples (Expression ratio (95% CI) 4.5 (1.16-17.4), adjusted P value = 0.029). Then, we depicted ROC curves for SLC1A1, LINC01231, RYR2 and lnc-SLC25A12 transcripts showing diagnostic power of 0.68, 0.75, 0.67 and 0.59, respectively. CONCLUSION: To sum up, the current study displays possible role of calcium related genes and lncRNAs in the development of ASD.

Association Between rs217727 and rs2839698 H19 Polymorphisms and Obesity.

Obesity is a worldwide health problem with an increasing trend. This condition has a significant genetic background. H19 lncRNA has been shown to protect from dietary obesity through decreasing levels of monoallelic genes in brown fat. In the current study, we aimed to find the association between two possibly functional H19 polymorphisms, namely rs217727 and rs2839698 and obesity in Iranian population. These polymorphisms have been shown to affect risk of some obesity-related conditions in different populations. The study included 414 obese cases and 392 controls. Notably, both rs2839698 and rs217727 were associated with obesity in the allelic model as well as all supposed inheritance models. In addition, after adjustment for gender, all P values remained significant. For rs2839698, the OR (95% CI) for T allele vs. C allele was 3.29 (2.67-4.05) (P-value < 0.0001). In the co-dominant model, both TT and CT genotypes were found to confer risk of obesity compared with CC genotype (OR (95% CI)= 14.02 (8.39-23.43) and 9.45 (6.36-14.04), respectively). Similarly, combination of TT and CT genotypes had an OR (95% CI) = 10.32 (7.03-15.17) when compared with CC genotype. For rs217727, the T allele was found to exert a protective effect (OR (95% CI) = 0.6 (0.48-0.75)). Moreover, in the co-dominant model, OR (95% CI) values for TT and TC genotypes vs. CC genotype were 0.23 (0.11-0.46) and 0.65 (0.49-0.87), respectively. Taken together, H19 polymorphisms may affect risk of obesity in Iranian population. It is necessary to conduct functional studies to confirm a causal relationship between the rs217727 and rs2839698 polymorphisms and obesity.

A bioinformatics-based approach and expression assay for identification of dysregulated genes in pituitary adenoma.

Non-functioning pituitary adenomas (NFPAs) are a group of pituitary neuroendocrine tumors that are associated with morbidity. The exact pathophysiological process leading to this pathology is not known. Nerve growth factor (NGF) is a neurotropic factor that might be involved in this process. We used bioinformatics tools to analyze expression of genes in NFPA samples. Our analyses led to identification of NGF-related genes, namely ARC, ID1, and SH3GL3 - as well as one long non-coding RNA (lncRNA) called myocardial infarction associated transcript (MIAT). Then, we assessed their expression in NFPAs and their adjacent non-cancerous samples. While expression levels of SH3GL3 and MIAT were different between NFPA samples and control samples, expressions of ARC and ID1 were not meaningfully different between these two groups of specimens. SH3GL3 was over-expressed in NFPA samples compared with control samples (expression ratio (95% CI)= 8.22 (1.51-44.6), P value= 0.03). Similarly, expression of MIAT was higher in NFPAs compared with controls (expression ratio (95% CI)= 7.7 (1.7-33.6), P value= 0.009). Taken together, we validated the bioinformatics results regarding the expression of SH3GL3 and MIAT. This study provides a deeper understanding of the involvement of these genes in the pituitary tumorigenesis.

Expression analysis of Treg-related lncRNAs in neuromyelitis optica spectrum disorder.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune condition affecting the central nervous system, in which various kinds of immune cells, including T and B cells, and numerous cytokines and chemokines are implicated. LncRNAs modulating the function or differentiation of regulatory T cells (Tregs) may be involved in the pathoetiology of NMO. To assess the involvement of these lncRNAs in this disease, we studied the expression levels of TH2-LCR, MAFTRR, NEST, RMRP, and FLICR in NMO patients and healthy subjects. All of the lncRNAs listed were up-regulated in NMO patients compared with healthy controls. Although the interaction of group and gender factors significantly affected the expression of NEST, RMRP, and TH2-LCR genes, we detected no effect of gender factor on the expression of the examined genes. The highest expression correlation was found between RMRP and TH2-LCR among cases with correlation coefficient 0.73. ROC curve analysis indicated that TH2-LCR, MAFTRR, RMRP, and FLICR had significant prospective diagnostic power (AUC ± SD = 0.99 ± 0.002, 0.97 ± 0.01, 0.91 ± 0.01 and 0.84 ± 0.04, respectively). Best of these genes was TH2-LCR with AUC ± SD = 0.99 ± 0.002, sensitivity= 0.97, specificity= 1, P-value= <0.0001. RMRP and TH2-LCR had a positive correlation with age and age at onset and a negative correlation with EDSS. Cumulatively, TH2-LCR, MAFTRR, RMRP, and FLICR lncRNAs, particularly TH2-LCR, could be considered as potential contributors to the pathogenesis of NMO disease.

Oleoylethanolamide protects mesenchymal stem/stromal cells (MSCs) from oxidative stress and reduces adipogenic related genes expression in adipose-derived MSCs undergoing adipocyte differentiation.

BACKGROUND: Human mesenchymal stem/stromal cells (hMSCs) are known for their pronounced therapeutic potential; however, they are still applied in limited clinical cases for several reasons. ROS-mediated oxidative stress is among the chief causes of post-transplantation apoptosis and death of hMSCs. It has been reported that a strategy to protect hMSCs against ROS is to pretreat them with antioxidants. Oleoylethanolamide (OEA) is a monounsaturated fatty acid derived from oleic acid and it has many protective properties, including anti-obesity, anti-inflammatory, and antioxidant effects. OEA is also used as a weight loss supplement; due to its high affinity for the PPAR-α receptor, OEA increases the fat metabolism rate. METHODS AND RESULTS: This study hence assessed the effects of OEA pretreatment on the in vitro survival rate and resistance of hMSCs under oxidative stress as well as the cellular and molecular events in the biology of stem/stromal cells affected by oxidative stress and free radicals. Considering the role of MSCs in adipogenesis and obesity, the expression of the main genes involved in adipogenesis was also addressed in this study. Results revealed that OEA increases the in vitro proliferation of MSCs and inhibits cell apoptosis by reducing the induction of oxidative stress. The results also indicated that OEA exerts its antioxidant properties by both activating the Nrf2/NQO-1/HO-1 signaling pathway and directly combating free radicals. Moreover, OEA can reduce adipogenesis through reducing the expression of PPARγ, leptin and CEBPA genes in hMSCs undergoing adipocyte differentiation. CONCLUSIONS: Thus, OEA protects hMSCs from oxidative stress and reduces adipogenic related genes expression and can be regarded as a therapeutic agent for this purpose.

Significant up-regulation of lncRNAs in neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an immune-related demyelinating defect. Long non-coding RNAs (lncRNAs) might influence the pathobiology and progression of NMOSD. The current study assessed expression level of NEAT1, PANDAR, MEG3 and TUG1 lncRNAs in the peripheral blood of NMOSD patients compared with healthy individuals. All mentioned lncRNAs were shown to be over-expressed in total NMOSD cases, male NMOSD cases and female NMOSD cases compared with the matching control subgroups. MEG3 had the most robust over-expression in patients subgroups compared with normal subjects. There was no noteworthy difference in the expression of any of lncRNAs between female and male patients. MEG3 had an ideal performance in the differentiation of NMOSD cases from healthy persons (Sensitivity and specificity values = 100%). Other lncRNAs could also efficiently separate NMOSD cases from control subjects (AUC values = 0.97, 0.89 and 0.88 for PANDAR, NEAT1 and TUG1, respectively). Cumulatively, NEAT1, PANDAR, MEG3 and TUG1 lncRNAs can be considered as appropriate disease markers for NMOSD.

Expression of cAMP and oxidative phosphorylation-related lncRNAs in non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) are benign lesions in the pituitary gland with important morbidities. In this study, based on a bioinformatics analysis to identify the genes and pathways that display significant differences between tumour tissues of NFPA patients and normal pituitary tissues, we selected lncRNAs related to cAMP and oxidative phosphorylation pathways, namely DNAH17-AS1, LINC00706 and SLC25A5-AS1. Then, we aimed to investigate by means of RT-qPCR, the expression of these lncRNAs along with two other lncRNAs, namely CADM3-AS1 and MIR7-3HG in NFPA samples compared to that in healthy tissues adjacent to the tumours. Transcripts of DNAH17-AS1, LINC00706 and MIR7-3HG were lower in NFPA samples compared with controls (Expression ratios (95% CI) = 0.43 (0.23-0.78), 0.58 (0.35-0.96) and 0.58 (0.35-0.96); p-values = 0.009, 0.025 and 0.036, respectively). AUC values of ROC curves of DNAH17-AS1, LINC00706 and MIR7-3HG were 0.62, 0.61 and 0.62, respectively. Expression of CADM3-AS1 was associated with the gender of patients in a way that it was lower in female patients (p-value = 0.04). The level of SLC25A5-AS1 was lower in subjects with disease duration lower than 1 year (p-value = 0.048). We showed dysregulation of three lncRNAs in NFPA tissues and potentiates these lncRNAs as important regulators of pathogenic events in these tumours.

Assessment of expression of calcium signaling related lncRNAs in epilepsy.

Calcium signaling is a metabolic pathway that is essential in neurons development and can be involved in the pathobiology of epilepsy. We assessed expression of three mRNA coding gene (SLC1A1, SLC25A12, and ATP2B2) and three related long non-coding RNAs (LINC01231:1, lnc-SLC25A12-8:1 and lnc-MTR-1:1) from this pathway in 39 patients with refractory epilepsy and 71 healthy controls. Expression of all genes except for lnc-SLC25A12 was higher in total epileptic cases compared with controls (P values = 0.0002, < 0.0001, < 0.0001, 0.049 and 0.0005 for SLC1A1, SLC25A12, LINC01231, ATP2B2 and lnc-MTR-1, respectively. When we separately compared expression of genes among males and females, SLC1A1, SLC25A12, LINC01231 and lnc-MTR-1 showed up-regulation in male cases compared with male controls. Moreover, expressions of SLC1A1 and SLC25A12 were higher in female cases compared with female controls. Remarkably, SLC25A12 was found to have the highest sensitivity value (= 1) for differentiation of epileptic cases from controls. Moreover, lnc-MTR-1 and lnc-SLC25A12 were sensitive markers for such purpose (sensitivity values = 0.89 and 0.87, respectively). The highest value belonged to LINC01231 with the value of 0.76. Taken together, this study demonstrates dysregulation of calcium-signaling related genes in epileptic patients and suggests these genes as potential biomarkers for epilepsy.

Associations between GRM7 polymorphisms and obesity in patients selected for sleeve gastrectomy.

Obesity is a worldwide problem in which genetic factors have a prominent role. We have selected two single nucleotide polymorphisms (SNPs) within glutamate metabotropic receptor 7 (GRM7) gene, namely rs6782011 and rs779867 to weigh their association with obesity in an Iranian cohort. The distribution of rs6782011 alleles was significantly different in the obese patients from normal controls (P < 0.0001; 434 obese patients vs. 297 normal controls). Distribution of alleles was also measured between sex-based groups of obese patients and controls. We detected remarkable differences between female obese cases and female control subjects (P < 0.0001; 374 female obese cases vs. 216 female normal controls); nevertheless, the difference in allele distribution was not significant for male cases compared with corresponding normal controls (p = 0.47; 60 male patients vs. 81 normal males). Contrariwise, distribution of rs779867 alleles was not significantly different between total obese patients compared with normal controls (P = 0.21; 434 obese patients vs. 297 normal BMI controls). There was also no significant difference for female and male obese patients compared with female and male normal BMI controls. Thus, GRM7 can be considered as a risk locus for obesity.

Expression analysis of PPAR-related lncRNAs in breast cancer.

Breast cancer is a genetically heterogeneous disorder associated with dysregulation of several genes. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that is expressed by many tumoral cells such as transformed breast cancer cells. We investigated expressions of nine PPARγ-related lncRNAs, namely KCNIP2-AS1, TRHDE-AS1, FAM13A-AS1, ALDH1A1-AS2, SH3BP5-AS1, HID1-AS1, LINC01140, LIPE-AS1 and ABCA9-AS1 in paired breast cancer samples and non-tumoral tissues. Expression assays showed lower expression levels of TRHDE-AS1, ALDH1L1-AS2, KCNIP2-AS1, ABCA9-AS1, LIPE-AS1 and LINC01140 in tumoral compared with non-tumoral samples. The mentioned genes could differentiate between breast tumors and non-tumoral samples with AUC values ranging from 0.77 to 0.62 for LINC01140 and LIPE-AS1, respectively. The highest specificity and sensitivity values were reported for KCNIP2-AS1 and LINC01140, respectively. Significant correlations were reported between all pairs of genes in both tumoral and non-tumoral tissues. The most robust ones were between ABCA9-AS1 and KCNIP2-AS1 (correlation coefficient=0.85) in non-tumoral tissues and between LIPE-AS1 and TRHDE-AS1 (correlation coefficient=0.83) in tumoral tissues. There was a significant negative association between expression levels of KCNIP2-AS1 gene in tumor tissues and different histological grades. Besides, there was a significant negative association between expression levels of FAM13A-AS1, KCNIP2-AS1and LIPE-AS1 genes in tumor tissues and different mitotic rates. Taken together, PPARγ-related lncRNAs might be regarded as potential contributors to the pathogenesis of breast cancer.

Expression analysis of cytoskeleton regulator RNA and Cyclin Dependent Kinase Inhibitor 2B genes in breast cancer.

BACKGROUND: Breast cancer has been found to be associated with deregulation of several non-coding genes and mRNA coding genes. OBJECTIVE: To assess expressions of CYTOR and CDKN2B in breast cancer and adjacent samples and find their relevance with clinical data. METHODS: We enumerated expression level of CDKN2B and CYTOR in 43 newly diagnosed breast cancer samples and their adjacent specimens using real-time PCR method Expression data was judged using Wilcoxon matched-pairs signed rank test. RESULTS: CYTOR level was higher in tumors compared with adjacent tissues. Nevertheless, there was no difference in expression of CDKN2B between these two sets of tissues. ROC curve analysis showed that CYTOR levels can differentiate between tumoral and adjacent tissues with AUC, specificity and sensitivity values of 0.65, 37% and 92% (P= 0.017). There was a positive correlation between expression levels of CYTOR and CDKN2B genes in breast cancer tissues (r= 0.5 and P= 0.0008) as well as adjacent tissues (r= 0.79 and P< 0.0001). Relative expression level of CDKN2B in normal tissues was associated with clinical stage (P= 0.014). Moreover, relative expression level of CDKN2B in tumor tissues was associated with the body weight. There was no other association between expressions of CYTOR and CDKN2B and clinical or pathological variables. CONCLUSIONS: Cumulatively, this study offers evidence for involvement of these genes in the pathoetiology of breast cancer.

Expression pattern of lncRNAs in pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) are a group of pituitary tumors lacking manifestations linked to high hormone production, such as acromegaly and Cushing's syndrome. NFPA carcinogenesis depends on several molecular players. Long non-coding RNAs (lncRNAs) are a class of molecular players whose role in tumorigenesis has just recently been recognized. In the current study, we appraised expressions of 5 lncRNAs, namely FGD5-AS1, ATP6V0E2-AS1, ARHGAP5-AS1, WWC2-AS2 and EPB41L4A-AS1 in NFPAs versus their corresponding non-tumoral samples. Expressions of ATP6V0E2-AS1, EPB41L4A-AS1, FGD5-AS1 and WWC2-AS2 were significantly increased in NFPA samples compared with adjacent non-tumoral samples (P values = 0.037, 0.007, 0.008 and 0.03, respectively). However, expression of ARHGAP5-AS1 was not different between NFPA samples and controls (P value = 0.62). EPB41L4A-AS1 and FGD5-AS1 could discriminate between NFPA samples and adjacent non-tumoral samples (P values = 0.03 and 0.04, respectively). However, the AUC values were not appropriate. There was a significant positive association between age of NFPA patients and invasiveness of NFPA (χ2 = 4.24, P value = 0.039). Moreover, there was a significant positive association between diseases duration and CSF leak (χ2 = 11.4, p value = 0.023). Finally, there was a significant positive association between tumor size and Knosp classification (χ2 = 11.5, p value = 0.02) and invasiveness of NFPA (χ2 = 6.12, p value = 0.04). The current study provides information about dysregulation of lncRNAs in NFPAs and warrants additional studies in this field.

Dysregulation of PVT1 and NEAT1 lncRNAs in pituitary adenomas.

Pituitary adenomas are slow-growing tumors originated from the anterior part of pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). PVT1, TUG1, MALAT1, NEAT1 and GAS5 are among lncRNAs with important roles in the regulation of cell proliferation, cell apoptosis, cell differentiation and cell cycle transition. In the current study, we assessed expression levels of PVT1, TUG1, MALAT1, NEAT1 and GAS5 in the pituitary adenoma samples compared with adjacent non-cancerous samples to find their relevance with this type of tumors and their potential as diagnostic markers in these tumors. Expression of NEAT1 was significantly higher in total adenoma tissues (Expression ratio (95% CI)= 7.06 (2.31-21.4), P value= 0.02) and in non-functioning pituitary adenoma (NFPA) samples (Expression ratio (95% CI)= 8.5 (2.17-33.12), P value= 0.04) compared with corresponding controls. Although both lncRNAs had appropriate sensitivity values for discrimination of NFPAs from adjacent non-cancerous tissues (0.84 and 0.90 for PVT1 and NEAT1, respectively), the calculated AUC values were not adequate for either lncRNAs (0.63 ± 0.04 and 0.58 ± 0.04 for PVT1 and NEAT1, respectively). Therefore, NEAT1 and PVT1 lncRNAs are dysregulated in NFPA. The current study suggests the role of NEAT1 and PVT1 in the pathogenesis of NFPA.

Upregulation of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in non-functioning pituitary adenoma.

Long non-coding RNAs (lncRNAs) have been shown to be dysregulated in a variety of malignant and non-malignant lesions including non-functioning pituitary adenomas (NFPAs). In the current experimental study, we have selected six lncRNAs, namely MAPKAPK5-AS1, NUTM2B-AS1, ST7-AS1, LIFR-AS1, PXN-AS1 and URB1-AS1 to assess their expression in a cohort of Iranian patients with NFPA. MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 were shown to be over-expressed in NFPA tissues compared with control samples (Expression ratios (95% CI) = 10 (3.94-25.36), 11.22 (4.3-28.8) and 9.33 (4.12-21.12); p values < 0.0001, respectively). The depicted ROC curves showed the AUC values of 0.73, 0.80 and 0.73 for MAPKAPK5-AS1, PXN-AS1 and URB1-AS1, respectively. Relative expression level of PXN-AS1 was associated with tumour subtype (p value = 0.49). Besides, relative expression levels of MAPKAPK5-AS1 and LIFR-AS1 were associated with gender of patients (p values = 0.043 and 0.01, respectively). Cumulatively, the current study indicates the possible role of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in the pathogenesis of NFPAs.

Abnormal expression of MAPK14-related lncRNAs in the peripheral blood of patients with multiple sclerosis.

Introduction: Contribution of MAPK14 in the pathogenesis of multiple sclerosis (MS) has been proposed by several studies. Long non-coding RNA (lncRNA) have been suggested to be functionally linked with Mitogen-activated protein kinase 14 (MAPK14). Methods: Expression levels of MAPK14 and its associated lncRNAs were measured in the circulation of MS patients compared with control subjects. Results: Expression levels of NORAD and RAD51-AS1 were higher in total patients compared with controls (Expression ratio (95% CI) = 1.4 (1.04-1.89), P value = 0.015 and Expression ratio (95% CI) = 1.91 (1.43-2.6), P value = 0.0001, respectively). Conversely, ZNRD1ASP was under-expressed in cases compared with controls (Expression ratio (95% CI) = 0.61 (0.41-0.8), P value = 0.0005). In spite of the observed abnormal expression levels of these lncRNAs in the circulation of MS patients, their expressions were not correlated with Expanded Disability Status Scale (EDSS) score, disease duration or age at disease onset. Conclusion: To sum up, the current investigation shows dysregulation of MAPK14-related lncRNAs in MS patients.