Differential expression of cancer-related lncRNAs in different subtypes of pituitary adenomas.

Recent investigations have demonstrated abnormal expression of non-coding RNAs in pituitary adenomas. Cntribution of many lncRNAs to the pathogenesis of these tumors has not been evaluated yet. HOTTIP, ANRIL, PANDAR, PCGEM1 and HOTAIR are among lncRNAs with established roles in the pathogenesis of human cancers, particularly those originated from endocrine organs. The current study aims at assessment of expression of these lncRNAs in pituitary adenomas in comparison with the adjacent non-cancerous pituitary tissues. HOTAIR expression was absent from the majority of adenoma and non-tumoral samples. Expression of HOTTIP was significantly higher in non-functioning pituitary adenoma (NFPA) samples compared with paired normal samples (expression ratio (95 % CI)= 2.1 (1.13-2.1), P value=0.03). Expression of PANDAR was higher in total adenoma samples compared with paired normal samples (expression ratio (95 % CI)= 1.91 (1.16-3.13), P value=0.02). Expression of ANRIL was higher in NFPA samples compared with paired normal samples (expression ratio (95 % CI)= 1.94 (1.05-3.6), P value=0.048) and in total adenoma samples compared with paired normal samples (expression ratio (95 % CI)= 1.82 (1.11-2.98), P value=0.025). The current study raises the possibility of contribution of lncRNAs in the pathogenesis of at least some subtypes of pituitary adenomas and warrant further functional studies in this field.

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.

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.

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.

Expression analysis of cell cycle related lncRNAs in breast cancer tissues.

Cell cycle regulation is an important cellular function. Abnormal regulation of this process can cause cancer. Several genes are involved in this process. There is no comprehensive study on expression pattern of cell cycle related lncRNAs in breast cancer patients. In the current study, we evaluated expressions of LINC00668, PRDM16-DT, SNHG7 and CDKN2A in 42 pairs of breast cancer tissues and adjacent non-tumoral tissues. Expression of SNHG7 was significantly lower in tumoral tissues compared with non-tumoral tissues. However, expressions of LINC00668, PRDM16-DT and CDKN2A were not significantly different between these two sets of samples. Expression levels of SNHG7 could separate tumoral tissues from non-tumoral tissues with AUC value= 0.66, sensitivity= 61% and specificity= 73%. Expression of CDKN2A was associated with clinical stage (P value=0.01). Expression levels of LINC00668, PRDM16-DT, SNHG7 and CDKN2A were higher in estrogen receptor (ER) positive samples compared with ER negative ones (P values=0.044, 0.008, 0.002 and 0.022, respectively). Moreover, expression of SNHG7 was higher in progesterone receptor (PR) positive samples compared with PR negative ones (P value=0.02). Finally, expressions of PRDM16-DT, SNHG7 and CDKN2A were higher in HER2/neu positive samples compared with HER2/neu negative ones (P values=0.017, 0.02 and 0.021, respectively). Taken together, our study demonstrates possible roles of these genes in breast cancer and warrants further functional studies.

The impact of non-coding RNAs in the pathobiology of eye disorders.

Eye disorders are common disorders with significant effects on personal, economic, and social aspects of life. These disorders have a genetic background and are associated with dysregulation of non-coding RNAs. Three classes of these transcripts, namely long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) have established roles in the regulation of gene expression and pathoetiology of ocular disorders. H19, MEG3, BANCR, UCA1, HOTAIR, ANRIL, XIST and MIAT are among important lncRNAs in ocular disorders. CircRNAs from ZBTB44, HIPK3, circ-PSEN1, COL1A2, ZNF532 and FAM158A loci have also been found to affect pathoetiology of ocular disorders. Both lncRNAs and circRNAs can serve as molecular sponges for miRNAs. In this review, we searched PubMed and Google Scholar databases to find the research articles summarizing the impact of non-coding RNAs in ocular disorders. The results of these studies would help in identification of suitable targets for treatment of ocular disorders.

Expression analysis of Rho GTPase-related lncRNAs in breast cancer.

The Rho GTPases have prominent roles in cell cycle transition and cell migration. Some members of this family have been found to be mutated in cancers. Moreover, alterations in expression levels and/or activity of these proteins have been reported in many types of cancers. Thus, Rho GTPases are involved in the carcinogenesis. Rho GTPases regulate growth, motility, invasiveness and metastatic ability of breast cancer cells. Long non-coding RNAs (lncRNAs) have been revealed to exert significant effect in the regulation of these proteins via direct routes or through sequestering microRNAs that inhibit Rho GTPases. We aimed to assess expression levels of four Rho GTPase-related lncRNAs, namely NORAD, RAD51-AS1, NRAV and DANCR in breast cancer samples versus non-cancerous specimens from the same individuals. Expression levels of NORAD were shown to be elevated in tumoral tissues compared with non-tumoral tissues (Expression ratio (95% CI)= 5.85 (3.16-10.83), Standard error of mean (SEM)= 0.44, P value< 0.0001). NRAV expression was also higher in tumoral tissues compared with control tissues (Expression ratio=2.85 (1.52-5.35), SEM= 0.45, P value= 0.0013). Similar to these lncRNAs, RHOA was demonstrated to be up-regulated in malignant tissues (Expression ratio=6.58 (3.17-13.63), SEM= 0.52, P value< 0.0001). Although expression ratio values showed up-regulation of RAD51-AS1 and DANCR in cancerous tissues (Expression ratio (95% CI)= 2.2 (1.05-4.6) and 1.35 (0.72-2.53), respectively), P values did not reach significance level (P values=0.0706 and 0.3746, respectively). There were significant associations between expression level of NRAV gene in tumor tissues and a number of parameters including age, histological tumor grade and tubule formation. Taken together, the current study shows dysregulation of a number of RHOA-related lncRNAs in breast cancer in association with abnormal up-regulation of this member of Rho GTPase family and suggests conduction of additional functional studies to unravel their mode of participation in the breast carcinogenesis.

Expression analysis of autophagy-related long non-coding RNAs in Iranian patients with breast cancer.

Autophagy has an established role in the development and progression of breast cancer. Recent studies have shown functional links between long non-coding RNAs (lncRNAs) and autophagy process. LINC01963, AL132989.1, RAB11B-AS1, PLBD1-AS1, AL139158.2, LOC105376805 (BX284668.5) and HERPUD2-AS1 (AC018647.2) are among autophagy related lncRNAs. In the current study, we compared expression of these seven lncRNAs between breast cancer samples and their paired non-cancerous tissues. RAB11B-AS1, HERPUD2-AS1 and PLBD1-AS1 were up-regulated in tumor samples compared with non-tumoral samples (Expression ratios (95% CI) = 2.56 (1.22-5.36), 2.13 (1.02-4.43) and 21.3 (10.36-43.89), respectively). ROC curve analysis indicated that PLBD1-AS1, RAB11B-AS1 and HERPUD2-AS1 had AUC values of 0.78, 0.61 and 0.6 for separation of breast cancer tissues from controls. Expression level of AL132989.1 in tumor tissues was associated with tubule formation (P value=0.02) in a way that tumor tissues with tubular formation score 1 had lower expression of AL132989.1. There was also a significant difference between expression levels of AL139158.2.1 among tumor tissues with different clinical stages (P value=0.02). Tumor tissues with higher clinical stages showed decreased expression of AL139158.2.1. In addition, there was also a significant difference between expression level of HERPUD2-AS1 in tumor tissues with different histological tumor grade and tubule formation (P value=0.03 and 0.003, respectively). Tumor tissues with higher histological tumor grade and higher tubule formation score showed higher expression of HERPUD2-AS1. Taken together, this study provides evidence for contribution of a number of recently identified autophagy-related lncRNAs in the pathogenesis of breast cancer.