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.

Non-coding RNA in SARS-CoV-2: Progress toward therapeutic significance.

The recently developed pathogenic virus, SARS-CoV-2, was found in the Hubei Province, China. Giving rise to a broad spectrum of symptoms, SARS-CoV-2 rapidly spread across the globe, causing multi-systemic and dangerous complications, with death in extreme cases. Thereby, the number of research cases increases every day on preventing infection and treating its resulting damage. Accumulating evidence suggests noncoding RNAs (ncRNAs) are necessary for modifying virus infection and antiviral immune reaction, along with biological processes regulating SARS-CoV-2 and subsequent disease states. Therefore, understanding these mechanisms might provide a further understanding of the pathogenesis and feasible therapy alternatives against SARS-CoV2. Consequently, the molecular biology of SARS-CoV-2, ncRNA's role in its infection, and various RNA therapy tactics against the virus have been presented in this review section.

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 assessment of a panel of long non-coding RNAs in gastric malignancy.

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.

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.

Expression analysis of NF-κB interacting long noncoding RNAs in breast cancer.

The nuclear factor-κB (NF-κB) has a prominent role in development of breast cancer and response of patients to conventional therapies. Several factors regulate the activity of this transcription factor. In the current investigation, we compared expression levels of five long non-coding RNAs (lncRNAs) with putative interactions with NF-κB namely CHAST, ADINR, DICER1-AS1, HNF1A-AS1 and NKILA between 78 breast cancer tissues and their paired adjacent non-cancerous tissues (ANCTs). We also assessed expression levels of ATG5 and CEBPA mRNA coding genes that are functionally linked with NF-κB signaling in these two sets of samples. All assessed genes except for NKILA were significantly down-regulated in tumoral tissues compared with ANCTs. Expression of NKILA was not significantly different between tumoral tissues and ANCTs. Expression levels of CEBPA and HNF1A-AS were significantly associated with cancer stage (P values of 0.03 and 0.02 respectively). Expression levels of ATG5 tended to be associated with mitotic rate (P = .05). The association between expression levels of ATG5 and tumor size was also significant (P = .02). Expression of CHAST was significantly associated with PR status (P = .04) and tended to be associated with ER status (P = .05). Finally, expression of NKILA was significantly associated with first pregnancy age (P = .01). No other significant association was detected between expression levels of assessed genes and clinical parameters. Expression levels of mentioned genes were significantly correlated with each other. The most significant correlations were found between CHAST and ADINR (correlation coefficients of 0.78 and 0.69 in tumoral tissues and ANCTs respectively). Based on the area under curve (AUC) values, DICER1-AS and CEBPA had the best performance in differentiation of tumoral tissues from ANCTs (AUC values of 0.92 and 0.90 respectively. Combination of transcript quantities of six genes could differentiate these two sets of samples with 92.3% sensitivity, 91% specificity and diagnostic power of 95%. The current project highlights dysregulation of NF-κB-associated genes in breast cancer tissues and suggests them as potential diagnostic markers in breast cancer.

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.

The Expression of CCAT2, UCA1, PANDA and GHET1 Long Non-coding RNAs in Lung Cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been considered to be prospective biomarkers for diagnosing lung cancer due to the fundamental roles they hold in the regulating several cancer-related pathways. METHODS: Using the quantitative real-time polymerase chain reaction method, we evaluated the expression of CCAT2, UCA1, PANDA and GHET1 lncRNAs in 32 lung cancer tissue samples and their corresponding adjacent non-cancerous tissues (ANCTs) from lung cancer patients admitted to the Labbafi-Nejad Hospital from 2015 to 2016. RESULTS: No significant differences were found in the expression of lncRNAs within the tumoral and non-tumoral tissue samples. Bayesian Multilevel analysis showed no association between the expression of lncRNAs and the patient's tumor node metastasis (TNM) stage following adjustments for age. Spearman correlation analysis revealed an inverse correlation between the expression of PANDA in tumoral tissues and age. Additionally, the difference in CCAT2 expression among the tumoral and non-tumoral tissues was inversely correlated with patients' age. Significant pairwise correlations were found between the expression of lncRNAs in both the tumoral and non-tumoral tissues. CONCLUSION: Despite the findings supporting a role for the lncRNAs, CCAT2, UCA1, PANDA and GHET1 in the pathogenesis of lung cancer, our data suggests no relationship for expression of these lncRNAs in lung cancer, questioning their potential as lung cancer biomarkers.

Assessment of SGO1 and SGO1-AS1 contribution in breast 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.

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.

AFAP1 and its naturally occurring antisense RNA are downregulated in gastric cancer samples.

Actin filament-associated protein 1 (AFAP1) encodes a protein which is an SRC proto-oncogene, non-receptor tyrosine kinase binding partner. This protein alters actin filament integrity in reaction to cellular signals. A long non-coding RNA, namely AFAP1-antisense RNA 1 (AS1), is transcribed from the antisense strand of this gene and potentially regulates its expression. In the present study, the expression levels of these two genes were evaluated in 30 gastric cancer samples and adjacent non-cancerous tissues (ANCTs) to identify their importance in this type of human malignancy. These two genes were significantly downregulated in gastric tumor samples compared with ANCTs (expression ratio 0.26 and 0.36, P=0.001 and P=0.04 for AFAP1 and AFAP1-AS1, respectively). Relative expressions of these two genes were associated with the location of primary tumor, in that AFAP1 and AFAP1-AS1 were significantly downregulated in all cardia tumor types compared with their paired ANCTs (P=0.04 and P=0.001, respectively). There were indications of a significant association between the expression levels of AFAP1 and peritoneal invasion and smoking history (P=0.05). Additionally, a lower expression level of AFAP1 was detected in younger patients and in high grade tumor types compared with olders and low grade tumors respectively (P=0.01 and P=0.04, respectively) and significantly higher expression levels of AFAP1-AS1 in patients with lymphatic/vascular invasion compared with those without lymphatic/vascular invasion (P=0.01). Furthermore, significant pairwise correlations were identified between the transcript levels of these genes in tumoral tissues and ANCTs (P values<0.05). The diagnostic power of AFAP1 and AFAP1-AS1 in gastric cancer was calculated as area under the curve (AUC) 0.75 and 0.67, respectively. The combination of the transcript levels of these two genes significantly enhanced the diagnostic power compared with diagnostic power of each gene (AUC, 0.76; P<0.001). The present study demonstrates the dysregulation of AFAP1 and AFAP1-AS1 in gastric cancer tissues in association with the clinicopathological data of patients and demonstrates the potential of these genes as diagnostic biomarkers.

Long noncoding RNAs expression in gastric cancer.

Long noncoding RNAs (lncRNAs) have been involved in the pathogenesis of several human cancers including gastric cancer. In the current study, we selected five lncRNAs namely NEAT1, TUG1, PANDA, UCA1, and GHET1 to assess their expressions in gastric cancer samples compared with adjacent noncancerous tissues (ANCTs) from the same patients. Some previous reports have shown contribution of these lncRNAs in gastric cancer. However, we aimed to explore their associations with patients' clinicopathological data and their potential as diagnostic biomarkers. Significant associations were found between site of primary tumor and relative expression of all lncRNAs in cancer samples compared with ANCTs. Besides, GHET1 relative expression was associated with lymph node status. The diagnostic power of GHET1 was higher from other lncRNAs. Combination of GHET1, TUG1, UCA1, and PANDA increased the diagnostic power and significance (AUC = 0.8; P < 0.0001). The current study supports participation of lncRNAs in the pathogenesis of gastric cancer and highlights their potential as diagnostic biomarkers.

Expression of long non-coding RNAs (lncRNAs) has been dysregulated in non-small cell lung cancer tissues.

BACKGROUND: Non-small cell lung cancer (NSCLC) as the most frequent type of lung cancer is associated with extensive mortality. Researchers have studied the suitability of several molecules as biomarkers for early detection of this cancer. Long non-coding RNAs (lncRNAs) as the main regulators of gene expression have also been assessed in this regard. METHODS: In the present study, we compared expression level of Fas-antisense 1 (FAS-AS1), Growth Arrest Specific 5 (GAS5), PVT1, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), taurine upregulated gene 1 (TUG1) and TNFα and hnRNPL related immunoregulatory LincRNA (THRIL) in 32 NSCLC samples and their corresponding adjacent non-cancerous tissues (ANCTs). RESULTS: NEAT1 has been significantly over-expressed in NSCLC tissues obtained from male subjects compared with the corresponding ANCTs (Relative expression (REx) = 3.022, P = 0.019) but not in female subjects (P = 0.975). FAS-AS1 was significantly down-regulated in NSCLC tissues obtained from both males and females subjects compared with the corresponding ANCTs (REx = - 4.12 and - 3.14, P = 0.015 and 0.033 respectively). TUG1, GAS5, THRIL and HOTAIRM1 were significantly down-regulated in tumoral tissues obtained from male subjects compared with the corresponding ANCTs. CONCLUSIONS: The observed dysregulation of these lncRNAs in NSCLC tissues compared with the corresponding ANCTs warrants future studies to confirm the results of the current study in larger sample sizes to elaborate their role as cancer biomarkers.

ß-Secretase 1 and its Naturally Occurring Anti-Sense RNA are Down-Regulated in Gastric Cancer.

ß-secretase (BACE1) and its naturally occurring anti-sense RNA (BACE1-AS) have established role in the pathologic process leading to Alzheimer's disease. Their possible implication in the neoangiogenesis suggests that they might be involved in the tumorigenesis events as well. In the present study, we compared transcript levels of these genes in 30 gastric cancer samples and their adjacent non-cancerous tissues (ANCTs) to find whether their altered expression might facilitate discrimination of these two sets of samples. Expressions of both genes were associated with site of primary tumor. Both genes were significantly down-regulated in tumoral tissues compared with ANCTs. Significant correlations were detected between transcript levels of these genes in both sets of samples. Transcript levels of BACE1 and BACE1-AS had the diagnostic power of 75% based on Receiver operating characteristic curve analysis. The current study provides evidences for contribution of BACE1 and BACE1-AS in gastric cancer evolution and suggests their potential as diagnostic markers.

Expression Analysis of OIP5-AS1 in Non-Small Cell Lung Cancer.

BACKGROUND: Lung cancer as the most fatal cancer of men has prompted researchers to find biomarkers for early detection and prognosis. Among the possible biomarkers are a group of non-coding transcripts with sizes more than 200 nucleotides called long non-coding RNAs (lncRNAs). AIMS: In the present study, we evaluated the expression levels of the lncRNA OIP5 antisense RNA 1 (OIP5-AS1) in 32 non-small cell lung cancer (NSCLC) samples compared with their corresponding adjacent non-cancerous tissue (ANCTs) by means of real-time polymerase chain reaction. The samples were obtained from patients who were admitted at Labbafi-Nejad Hospital during 2015 and 2016. RESULTS: OIP5-AS expression levels was significantly decreased in tumoral tissues compared with ANCTs in total samples and in male subgroup. However, no association was found between relative expression of OIP5-AS1 and clinicopathological data of patients or history of smoking. Expression levels of this lncRNA were not correlated with patients age. CONCLUSIONS: This lncRNA is possibly a novel biomarker of NSCLC in Iranian patients. Future studies are needed to confirm the results of our study in larger sample sizes. Moreover, based on the difference in lung cancer associated risk factors in different populations, population-based studies are needed to explore the role of this lncRNA in the pathogenesis of cancers in each region to design appropriate targeted therapies for each population. Key words: lung cancer - OIP5-AS - lncRNA - long non-coding RNA.

Fas-Antisense Long Noncoding RNA and Acute Myeloid Leukemia: Is There any Relation?

In recent years, lncRNAs have been considered as potential predictive biomarkers for prognosis of different human cancers. One example is the FAS antisense RNA 1 (FAS-AS1) located in the 10q23.31 region which is transcribed from the opposite strand of the FAS gene. FAS has an important role in regulation of apoptotic pathways and there is an inverse correlation between FAS-AS1 expression level and production of the soluble form of Fas, so that it might have potential as a therapeutic target to improve chemotherapy effectiveness. In the present study we therefore evaluated FAS-AS1 expression in blood samples of de novo AML patients and healthy controls using real-time quantitative reverse transcription-PCR (qRT-PCR). Our results indicated that the expression level of FAS-AS1 lncRNA demonstrated no significant difference between AML patients and healthy individuals. We conclude from the obtained data that FAS-AS1 is not an informative and reliable biomarker for AML diagnosis, although our results need to be confirmed in further studies.