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.

In silico characterization of competing endogenous RNA network in glioblastoma multiforme with a systems biology approach.

Glioblastoma multiforme (GBM) is the most frequent malignant type of primary brain cancers and is a malignancy with poor prognosis. Thus, it is necessary to find novel therapeutic modalities based on molecular events occur at different stages of tumor progression. We used expression profiles of GBM tissues that contained long non-coding RNA (lncRNA), microRNA (miRNA) and mRNA signatures to make putative ceRNA networks. Our strategy led to identification of 1080 DEmRNAs, including 777 downregulated DEmRNAs (such as GJB6 and SLC12A5) and 303 upregulated DEmRNAs (such as TOP2A and RRM2), 19 DElncRNAs, including 16 downregulated DElncRNAs (such as MIR7-3HG and MIR124-2HG) and 3 upregulated DElncRNAs (such as CRNDE and XIST) and 49 DEmiRNAs, including 10 downregulated DEmiRNAs (such as hsa-miR-10b-5p and hsa-miR-1290) and 39 upregulated DEmiRNAs (such as hsa-miR-219a-2-3p and hsa-miR-338-5p). We also identified DGCR5, MIAT, hsa-miR-129-5p, XIST, hsa-miR-128-3p, PART1, hsa-miR-10b-5p, LY86-AS1, CRNDE, and DLX6-AS1 as 10 hub genes in the ceRNA network. The current study provides novel insight into molecular events during GBM pathogenesis. The identified molecules can be used as therapeutic targets for GBM.

Expression pattern of non-coding RNAs in non-functioning pituitary adenoma.

Non-functioning pituitary adenoma (NFPA) is a benign tumor arising from the adenohypophyseal cells. They can be associated with symptoms arising from mass effect. Although these tumors are regarded to be benign tumors, they are associated with increased comorbidity and mortality. Several studies have indicated abnormal expression of genes in these tumors. In the current study, we have used existing methods to identify differentially expressed genes (DEGs) including DE long non-coding RNAs (DElncRNAs) and DE microRNAs (DEmiRNAs) in NFPAs compared with normal samples. Then, we have assessed the relation between these genes and important signaling pathways. Our analyses led to identification of 3131 DEGs, including 189 downregulated DEGs (such as RPS4Y1 and DDX3Y) and 2898 upregulated DEGs (such as ASB3 and DRD4), and 44 DElncRNAs, including 8 downregulated DElncRNAs (such as NUTM2B-AS1 and MALAT1) and 36 upregulated DElncRNAs (such as BCAR4 and SRD5A3-AS1). GnRH signaling pathway, Tight junction, Gap junction, Melanogenesis, DNA replication, Nucleotide excision repair, Mismatch repair and N-Glycan biosynthesis have been among dysregulated pathways in NFPAs. Taken together, our study has revealed differential expression of several genes and signaling pathways in this type of tumors.

Assessment of expression of oxytocin-related lncRNAs in schizophrenia.

BACKGROUND: Schizophrenia is a neuropsychiatric disorder characterized by a variety of clinical manifestations. This disorder has a complex inheritance. Oxytocinegic system has been shown to be implicated in the pathophysiology of schizophrenia. This system can alter social cognition through direct interaction with dopaminergic signaling, facilitating brain-stimulation reward, reduction of defense mechanism and stress reactivity, and modulation of social information processing through enhancing the greatness of social incentives. Long non-coding RNAs (lncRNAs) can affect activity of oxytocinegic system, thus contributing in the etiology of this disorder. METHODS: We designed the current study to appraise dysregulation of nine oxytocin-associated mRNAs and lncRNAs in the venous blood of patients with schizophrenia. RESULTS: Expression of FOS was up-regulated in total patients compared with total control group (Expression ratio (95% CI)= 13.64 (5.46-34.05), adjusted P value<0.0001) and in female patients compared with female control group (Expression ratio (95% CI)=32.13 (5.81-176), adjusted P value<0.0001). Such pattern was also seen for Lnc-FOXF1 (Expression ratio (95% CI)= 6.41 (2.84-14.3), adjusted P value<0.0001 and Expression ratio (95% CI)= 14.41 (3.2-64.44), adjusted P value<0.0001, respectively). ITPR1 was down-regulated in total patients compared with total controls (Expression ratio (95% CI)= 0.22 (0.076-0.67), adjusted P value=0.0079). ROC curve analyses demonstrated that FOS had the best AUC value among other genes in differentiation between patients and controls (AUC=0.78). CONCLUSION: The above-mentioned results imply dysregulation of oxytocin-related genes in the circulatory blood of patients with schizophrenia.

Expression analysis of IFNAR1 and TYK2 transcripts in COVID-19 patients.

As a member of JAK family of non-receptor tyrosine kinases, TYK2 has a crucial role in regulation of immune responses. This protein has a crucial role in constant expression of IFNAR1 on surface of cells and initiation of type I IFN signaling. In the current study, we measured expression of IFNAR1 and TYK2 levels in venous blood samples of COVID-19 patients and matched controls. TYK2 was significantly down-regulated in male patients compared with male controls (RME = 0.34, P value = 0.03). Though, levels of TYK2 were not different between female cases and female controls, or between ICU-admitted and non-ICU-admitted cases. Expression of IFNAR1 was not different either between COVID-19 cases and controls or between patients required ICU admission and non-ICU-admitted cases. However, none of these transcripts can properly diffrentiate COVID-19 cases from controls or separate patients based on disease severity. The current study proposes down-regulation of TYK2 as a molecular mechanism for incapacity of SARS-CoV-2 in induction of a competent IFN response.