CircRNA-associated ceRNA networks (circCeNETs) in chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD), a chronic airway disorder, which is mostly brought on by cigarette smoke extract (CSE), is a leading cause of death which has a high frequency. In COPD patients, smoking cigarette could also trigger the epithelial-mesenchymal transition (EMT) of airway remodeling. One of the most significant elements of environmental contaminants that is linked to pulmonary damage is fine particulate matter (PM2.5). However, the basic processes of lung injury brought on by environmental contaminants and cigarette smoke are poorly understood, particularly the molecular pathways involved in inflammation. For the clinical management of COPD, investigating the molecular process and identifying workable biomarkers will be important. According to newly available research, circular RNAs (circRNAs) are aberrantly produced and serve as important regulators in the pathological processes of COPD. This class of non-coding RNAs (ncRNAs) functions as microRNA (miRNA) sponges to control the levels of gene expression, changing cellular phenotypes and advancing disease. These findings led us to concentrate our attention in this review on new studies about the regulatory mechanism and potential roles of circRNA-associated ceRNA networks (circCeNETs) in COPD.

The potential roles of Th17 cells in the pathogenesis of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated chronic autoimmune disease, whose pathogenesis and etiology are not entirely understood. OLP is characterized by subepithelial lymphocyte infiltration and elevated intra-epithelial lymphocytes. The majority of lamina propria lymphocytes are CD4+ T cells. CD4+ helper T (Th) cells play a crucial role in activating CD8+ cytotoxic T cells (CTLs) through interactions and cytokine production. Th1 and Th2 cells are well-accepted to be associated with OLP pathogenesis. However, OLP treatment is challenging yet, the more information we have about the pathology of OLP, the easier it will be treated. With the discovery of Th17 cells in recent years and the demonstration of their role in autoimmune disease, many researchers started to investigate the role of Th17 in the pathogenesis of OLP. METHODS: To make up this review, studies covering the role of TH17 in different types of lichen planus were selected from major databases. RESULTS: As we review in this article, Th17 cells and their signature cytokines play an important role in OLP pathogenesis. As well, utilizing some anti-IL-17 antibodies showed promising results in improving the disease; however, more studies are still needed to better understand and treat OLP.

Anticancer traits of chimeric antigen receptors (CARs)-Natural Killer (NK) cells as novel approaches for melanoma treatment.

Owing to non-responsiveness of a high number of patients to the common melanoma therapies, seeking novel approaches seem as an unmet requirement. Chimeric antigen receptor (CAR) T cells were initially employed against recurrent or refractory B cell malignancies. However, advanced stages or pretreated patients have insufficient T cells (lymphopenia) amount for collection and clinical application. Additionally, this process is time-consuming and logistically cumbersome. Another limitation of this approach is toxicity and cytokine release syndrome (CRS) progress and neurotoxicity syndrome (NS). Natural killer (NK) cells are a versatile component of the innate immunity and have several advantages over T cells in the application for therapies such as availability, unique biological features, safety profile, cost effectiveness and higher tissue residence. Additionally, CAR NK cells do not develop Graft-versus-host disease (GvHD) and are independent of host HLA genotype. Notably, the NK cells number and activity is affected in the tumor microenvironment (TME), paving the way for developing novel approaches by enhancing their maturation and functionality. The CAR NK cells short lifespan is a double edge sword declining toxicity and reducing their persistence. Bispecific and Trispecific Killer Cell Engagers (BiKE and Trike, respectively) are emerging and promising immunotherapies for efficient antibody dependent cell cytotoxicity (ADCC). CAR NK cells have some limitations in terms of expanding and transducing NK cells from donors to achieve clinical response. Clinical trials are in scarcity regarding the CAR NK cell-based cancer therapies. The CAR NK cells short life span following irradiation before infusion limits their efficiency inhibiting their in vivo expansion. The CAR NK cells efficacy enhancement in terms of lifespan TME preparation and stability is a goal for melanoma treatment. Combination therapies using CAR NK cells and chemotherapy can also overcome therapy limitations.

Purinergic receptors are a key bottleneck in tumor metabolic reprogramming: The prime suspect in cancer therapeutic resistance.

ATP and other nucleoside phosphates have specific receptors named purinergic receptors. Purinergic receptors and ectonucleotidases regulate various signaling pathways that play a role in physiological and pathological processes. Extracellular ATP in the tumor microenvironment (TME) has a higher level than in normal tissues and plays a role in cancer cell growth, survival, angiogenesis, metastasis, and drug resistance. In this review, we investigated the role of purinergic receptors in the development of resistance to therapy through changes in tumor cell metabolism. When a cell transforms to neoplasia, its metabolic processes change. The metabolic reprogramming modified metabolic feature of the TME, that can cause impeding immune surveillance and promote cancer growth. The purinergic receptors contribute to therapy resistance by modifying cancer cells' glucose, lipid, and amino acid metabolism. Limiting the energy supply of cancer cells is one approach to overcoming resistance. Glycolysis inhibitors which reduce intracellular ATP levels may make cancer cells more susceptible to anti-cancer therapies. The loss of the P2X7R through glucose intolerance and decreased fatty acid metabolism reduces therapeutic resistance. Potential metabolic blockers that can be employed in combination with other therapies will aid in the discovery of new anti-cancer immunotherapy to overcome therapy resistance. Therefore, therapeutic interventions that are considered to inhibit cancer cell metabolism and purinergic receptors simultaneously can potentially reduce resistance to treatment.

Circular RNA-associated ceRNA network involved in HIF-1 signalling in triple-negative breast cancer: circ_0047303 as a potential key regulator.

The aggressive and highly metastatic nature of triple-negative breast cancer (TNBC) causes patients to suffer from the poor outcome. HIF-1 signalling pathway is a prominent pathway that contributes to angiogenesis and metastasis progression in tumours. On the contrary, the undeniable importance of circular RNAs (circRNAs) as multifunctional non-coding RNAs (ncRNAs) has been identified in breast cancer. These ncRNAs owing to their high stability and specificity have been becoming a hotspot in cancer researches. circRNAs act as competing endogenous RNAs (ceRNAs) and compete with mRNAs for shared miRNAs, thus modulate gene expression. Since the most dysregulated biological functions in TNBC are associated with cellular invasion, understanding the molecular pathogenesis of these processes is a crucial step towards the development of new treatment approaches. The purpose of this study is to undermine the circRNA-associated ceRNA network involved in HIF-1 signalling in TNBC using an integrative bioinformatics approach. In the next step, the novel circ_0047303-mediated ceRNA regulatory axes have been extracted and validated across TNBC samples. We show that circ_0047303 has the highest degree in the circRNA-associated ceRNA network and shows a significant up-expression in TNBC. Moreover, our results suggest that circ_0047303 could mediate the upregulation of key angiogenesis-related genes, including HIF-1, EIF4E2 and VEGFA in TNBC through sponging the tumour-suppressive miRNAs. The circ_0047303 could be a promising molecular biomarker and/or therapeutic target for TNBC.

Breast cancer-linked lncRNA u-Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding.

Recently, it has been revealed that estrogen-related reproductive factors are linked with some early gene expression lesions associated with malignancy in clinically healthy breasts. Accordingly, the aim of the current study was to evaluate the association of expression levels of estrogen-related long noncoding RNAs (lncRNAs) upstream Eleanor (u-Eleanor) and HOX antisense intergenic RNA (HOTAIR) with the different patterns of reproductive factors in breast tissue of healthy women. The subjects of this study were 98 cancer-free women who had undergone cosmetic mammoplasty. The expression levels of u-Eleanor and HOTAIR were measured using quantitative real-time polymerase chain reaction. The results of the current study showed that the women without a history of breastfeeding had a high-level expression of u-Eleanor compared with the women with a breastfeeding duration greater than 6 to 24 months (P = 0.03) as well as the women with a breastfeeding duration of more than 24 months (P = 0.005). Furthermore, a higher expression of u-Eleanor was found in the women with a short breastfeeding duration for 1 to 6 months than that in the women with a breastfeeding duration of greater than 24 months (P = 0.02). In the same way, the results of correlation test (r = -0.258; P = 0.036) and multivariate regression model (ß = -0.321; P = 0.023) are indicative of a significant relationship of elevated expression of u-Eleanor with decreasing breastfeeding duration in the women. These findings could be important to identify the molecular mechanisms behind the relationship between a lack or short duration of the breastfeeding and the risk of breast cancer, which has previously been reported by epidemiological studies.

Expression levels of breast cancer-related GAS5 and LSINCT5 lncRNAs in cancer-free breast tissue: Molecular associations with age at menarche and obesity.

Long noncoding RNAs (lncRNAs) constitute a major class of the human transcriptome which play crucial roles in the key biological processes of both normal and malignant breast cells. Although the aberrant expression of lncRNAs has been well-documented in breast cancer (BC), little is currently known about the association between their expression levels in the breast tissue of healthy women and BC risk factors, especially the reproductive or demographic characteristics that are among the most well-known BC risk modifiers. This study was an attempt to investigate the correlation between the expression levels of 2 breast cancer-related lncRNAs, including GAS5 and LSINCT5, and reproductive and demographic characteristics in 145 normal breast tissues that were obtained from women without breast cancer undergoing cosmetic surgery. Total RNA was extracted from fresh normal breast tissues, and the expression level of target lncRNAs was quantified using real-time qPCR. Differences in the mean normalized gene expression among the subgroups of different variables were analyzed. The expression levels of both genes was lower in the overweight-obese (BMI ≥ 25) subgroup than that in the normal BMI (BMI < 25) subgroup (GAS5 P = .019, LSINCT5 P = .036). Moreover, the expression level of GAS5 was negatively correlated with BMI (r: -.170, P: .041). The expression level of GAS5 was higher in women with late menarche (>13 years) than that with early menarche (≤13 years; P = .017). These findings may assist to obtain insights into the molecular mechanisms through which the reproductive or obesity-related estrogen changes contribute to the breast carcinogenesis. In conclusion, this study presents the first evidence for the presence of a link between the lncRNA expression and the reproductive or obesity related factors in the breast tissue of healthy women.

The SDF1 A/G Gene Variant: A Susceptibility Variant for Myocardial Infarction.

BACKGROUND: Although environmental factors play an important role in susceptibility to myocardial infarction (MI), genetic determinants also provide a significant contribution. This study aimed to determine whether or not MI susceptibility is influenced by the SDF1-rs1801157A/G and HHEX-rs1111875 A/G polymorphisms in an Iranian population. METHODS: A total of 120 patients with MI and 120 healthy controls were enrolled. Blood samples were collected from all the participants for genomic DNA extraction and testing. Polymorphism genotyping was determined by the polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: Multiple logistic regression analysis revealed that the A allele and AA genotype of the SDF1-rs1111875 polymorphism produce a significant risk of MI both before (crude odds ratio [OR] = 8.83, 95% confidence interval [95% CI] = 1.05-73.76, p = 0.025) and after adjustment (adjusted OR = 8.12, 95% CI = 5.02-19.42, p = 0.04). In contrast, the GG genotype of the SDF1-rs1111875 polymorphism provides a protective effect on MI in a recessive model (GG vs. AA+AG) before (crude OR = 0.57, 95% CI = 0.34-0.97, p = 0.037) and after adjustment (adjusted OR = 0.53, 95% CI = 0.3-0.82, p = 0.021). No association was found between the HHEX-rs1111875 A/G polymorphism alleles and the susceptibility to MI. CONCLUSION: Taken together, the current findings suggest that the SDF1-rs1801157A/G gene variant may play an important role in relation to MI in this Iranian population. Nevertheless, more replication studies and meta-analyses should be carried out in this area.

Influences of IL-1b-3953 C>T and MMP-9-1562C >T Gene Variants on Myocardial Infarction Susceptibility in a Subset of the Iranian Population.

AIMS: IL-1b-3953 C>T and MMP-9-1562C>T variants have been shown to be linked to the development of myocardial infarction (MI), although previous studies have reported inconsistent results. The aim of the present study was to determine whether these genetic variations are associated with MI susceptibility in an Iranian population. METHODS: In the current study, 117 patients with MI and 120 control group members were selected as participants. Peripheral blood samples were taken from all the subjects for genomic DNA extraction. Single nucleotide polymorphism (SNP) genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. RESULTS: Multiple logistic regression analysis revealed that the TT genotype of the IL-1b-3953 C>T polymorphism is associated with a significant MI protective effect in: the homozygote model after adjustment for MI risk factors (odds ratio [OR]: 0.18, confidence interval [95% CI] = 0.04-0.72; p = 0.01); and also in the recessive genetic model both before (OR: 0.39, 95% CI: 0.15-0.96, p = 0.04) and after (OR: 0.15, 95% CI: 0.04-0.58, p = 0.006) adjustment for MI risk factors. Furthermore, multiple logistic regression analysis indicated that the individuals with the TT genotype of the MMP-9-1562C>T polymorphism were significantly protected against MI in comparison with the CC genotype (OR: 0.01, 95% CI: 0.002-0.68, p = 0.03). CONCLUSION: The findings suggest that the minor alleles of the two polymorphisms under study both have protective effects with respect to MI susceptibility in the Iranian population.