Investigating SNHG3 and BCYRN1 lncRnas expression in the peripheral blood cells of multiple sclerosis patients.

BACKGROUND: MS (Multiple sclerosis) is a progressive neurologic disorder often appearing in the third decade of life. MS is the most frequent demyelinating disease of the central nervous system. The development of MS is influenced by environmental, genetic, and epigenetic factors. The bulk of the human transcriptome comprises lncRNAs, which play crucial regulatory roles. We aimed to assess the SNHG3 and BCYRN1 lncRNA expression in blood samples from MS patients and how these lncRNAs and disease activity are related. METHODS: A total of 100 MS patients, including 8 primary progressive (PP), 82 relapsing-remitting (RR), and 10 secondary progressive (SP) MS, as well as 100 healthy controls, had their blood samples taken. Gene expression was assessed using quantitative real-time PCR. Recognizing the receiver operating characteristic (ROC) curve analysis, the diagnostic potential of lncRNA levels was evaluated. RESULTS: Expressions of SNHG3 and BCYRN1 were found to have significantly increased (p < 0.0001). SNHG3 expression level showed significant differences compared to age groups and MS subtypes (p value = 0.001 and p value = 0.02).Furthermore, patients with a family history showed elevated BCYRN1 expression with a p value of 0.01. Considering the age factor, BCYRN1 exhibits altered expression levels in patient groups compared to healthy controls (p value 0.04). Additionally, the novel biomarkers SNHG3 and BCYRN1 can be used to diagnose MS (AUC = 0.97 and AUC = 0.88, respectively). DISCUSSION: Increased levels of SNHG3 and BCYRN1 in the serum may serve as potential molecular biomarkers for the MS diagnosis.

miRNA-21, an Important Regulator of Autoimmune Diseases.

miRNA-21 is regarded as both an abundant and highly conserved member of the microRNA (miRNA) family. It is expressed in virtually every cell and is responsible for critical regulatory actions that are important in health and disease. This microRNA has been shown to potentially have a role in the pathogenesis of several immune-related disorders, including autoimmune diseases, such as Multiple sclerosis and systemic lupus erythematosus, as two prominent examples of diseases that might be involved. In the current research, we looked at the role of miRNA-21, regarded as one of the most significant pathogenic miRNAs with a role in the development of autoimmune illness.

Autophagy Inhibition and Sensitization to Cisplatin in Esophageal Cancer Stem-Like Cells via All-trans Retinoic Acid-induced miR-30a.

AIM: Providing insights into the chemoresistance of esophageal squamous cell carcinoma (ESCC) and its dependence on chemotherapy-induced autophagy. BACKGROUND: Autophagy is induced during chemotherapy of cancer cells, promoting resistance to anti-cancer treatments. OBJECTIVE: The objective of this study is to investigate the modulation of microRNA-30a (miR-30a), a known regulator of autophagy, in ESCC cells by all-trans retinoic acid (ATRA). METHODS: Treatment involved ESCC cells KYSE-30 and TE8 with cis-dichloro-diamine platinum (CDDP), enriching CDDP-surviving cells (CDDP-SCs). qRT-PCR and dual luciferase reporter assay (DLRA) were employed to evaluate miR-30a expression and its interaction with Beclin-1 (BECN1) in both CDDP-SCs and those treated with ATRA. RESULTS: Chemotherapy using CDDP led to a significant decrease in miR-30a expression within ESCC cells. Increased autophagy levels were identified in cancer cells exhibiting stem cell-like properties, characterized by the overexpression of specific stem cell markers. These results suggest that the downregulation of miR-30a induced by CDDP treatment may represent a potential underlying mechanism for increased autophagic activity, as evidenced by the upregulation of autophagy-related proteins, such as BECN1 and an elevated LC3-II/LC3-I ratio. ATRA treatment elevated miR-30a expression and disrupted hallmark cancer stem cell (CSC) features in ESCC cells. Further investigations demonstrated that increased miR-30a expression led to a reduction in the expression of its target gene, BECN1, and attenuated BECN1-mediated autophagy. This resulted in an augmentation of CDDP-induced apoptosis in ESCC cells and a G2/M cell cycle arrest. CONCLUSION: CDDP chemotherapy reduced miR-30a, promoting ESCC cell resistance through autophagy and CSC-like features, a process that may be modulated by ATRA.

Serum Levels of Long Non-coding RNAs NEAT1, GAS5, and GAPLINC Altered in Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA), an autoimmune joint inflammatory disease, presents a significant challenge due to its prevalence, particularly among women, affecting around 6% of individuals over the age of 65. Novel insights into disease mechanisms are crucial for improved diagnostic and therapeutic approaches. OBJECTIVE: Long non-coding RNAs (lncRNAs) have emerged as potential contributors to the pathogenesis of various autoimmune diseases, including RA. This study aims to investigate the unique roles of four lncRNAs-NEAT1, GAS5, TMEVPG1, and GAPLINC-in the etiology of RA. METHODS: Leveraging isolated serum samples from RA patients and healthy controls, we comprehensively evaluated the expression profiles of these lncRNAs. RESULTS: Notably, our findings unveil a distinctive landscape of lncRNA expressions in RA. Among them, GAPLINC exhibited a significantly elevated average expression in the serum samples of RA patients, suggesting a potential biomarker candidate for disease stratification. Importantly, reduced expression of NEAT1 and GAS5 was observed in RA patients, highlighting their possible roles as diagnostic and prognostic markers. Conversely, TMEVPG1 displayed unaltered expression levels in RA samples. CONCLUSION: Our study introduces a novel dimension to RA research by identifying NEAT1, GAS5, and GAPLINC as promising serological biomarkers. These findings hold significant clinical implications, offering potential avenues for improved diagnosis, disease monitoring, and therapeutic interventions in RA.

Interferon Signature's Members, a Novel Altered Correlation upon Interferon-ß Treatment in Multiple Sclerosis Patients.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system and is characterized by extensive brain damage and neurodegeneration. Immunological, genetic, and histological analyses of MS patients provide data in support of the concept that autoimmunity plays a crucial role in the condition's course. It has been proposed that MS may be treated with interferon (IFN)-ß and other members of the type I family. OBJECTIVE: Low levels of type I IFN in MS patients may affect immunological control, establish the threshold for an IFN therapeutic response, and be"primed" or "fixed" by IFN therapy. METHODS: This study was conducted as a cross-sectional study. qRT-PCR was used to examine the expression of two critical IFN regulatory genes, IFI44 and MX1, in MS patients receiving IFN-ß treatment. RESULTS: The findings demonstrated a considerable rise in the expression of both genes in MS patients treated with IFN-ß compared to those newly diagnosed with the illness. In addition, IFI44 and MX1 might be positively associated with their expression after IFN-ß therapy and be regarded as IFN-ß responsiveness indicators. CONCLUSION: The IFI44/MX1 axis could act as one of the crucial regulators of the disease following IFN-ß treatment.

The effect of glatiramer acetate, IFNß-1a, fingolimod, and dimethyl fumarate on the expression of T-bet, IFN-γ, and MEG3 in PBMC of RRMS patients.

OBJECTIVE: Multiple sclerosis (MS) is a progressing neurodegenerative disease marked by chronic central nervous system inflammation and degeneration.This study investigates gene expression profiles of T-box transcription factor TBX21 (T-bet), interferon-gamma (IFN-γ), and long non-coding RNA MEG3 in peripheral blood mononuclear cells (PBMCs) from treatment-naïve Relapsing-Remitting Multiple Sclerosis patients (RRMS), healthy controls, and RRMS patients on different Disease Modifying Therapies (DMTs). The aim is to understand the role of T-bet, IFN-γ, and MEG3 in MS pathogenesis and their potential as diagnostic and therapeutic targets. RESULTS: Elevated T-bet expression is observed in treatment-naïve RRMS patients compared to healthy individuals. RRMS patients treated with Interferon beta-1alpha (IFNß-1a) and fingolimod exhibit downregulated T-bet and MEG3 expression levels, respectively, with more pronounced effects in females. Healthy individuals show a moderate positive correlation between T-bet and MEG3 and between IFN-γ and T-bet. In RRMS patients treated with Glatiramer Acetate (GA), a strong positive correlation is observed between MEG3 and IFN-γ. Remarkably, RRMS patients treated with Dimethyl Fumarate (DMF) exhibit a significant positive correlation between T-bet and MEG3. These findings underscore the diagnostic potential of T-bet in RRMS, warranting further exploration of MEG3, T-bet, and IFN-γ interplay in RRMS patients.

Rheumatoid arthritis and non-coding RNAs; how to trigger inflammation.

Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease categorized by continuous synovitis in the joints and systemic inflammatory responses that can cause lifelong disability. The major cause of RA is the dysregulation of the immune response. The development of RA disease includes multiplex association of several interleukins and cells, which leads to synovial cell growth, cartilage and bone damage. The primary stage of RA disease is related to the modification of both the innate and adaptive immune systems, which leads to the formation of autoantibodies. This process results in many damaged molecules and epitope spreading. Both the innate (e.g., dendritic cells, macrophages, and neutrophils) and acquired immune cells (e.g., T and B lymphocytes) will increase and continue the chronic inflammatory condition in the next stages of the RA disease. In recent years, non-coding RNAs have been proved as significant controllers of biological functions, especially immune cell expansion and reactions. Non-coding RNAs were primarily containing microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). Various studies confirmed non-coding RNAs as hopeful markers for diagnosing and curing RA. This review will describe and cover existing knowledge about RA pathogenesis, which might be favorable for discovering possible ncRNA markers for RA.

Changes in the Expression of Long Non-Coding RNA SDMGC and Its Target Gene, TRIM16, in Patients with Gastric Cancer.

PURPOSE: Gastric cancer (GC) has been identified worldwide as one of the most common cancer types with a high mortality rate. LncRNA SDMGC has been recognized as an oncogene with regulatory effects on its target gene, TRIM16, which is believed to play a tumor-suppressing role in various cancers. Both these genes are involved in GC development, tumorigenesis, invasion, and metastasis. The current study is aimed to investigate the association of SDMGC and TRIM16 with GC susceptibility and GC patients' clinicopathological characteristics. METHODS: A total of 100 GC tissues and their corresponding adjacent non-tumor tissues were sampled. Total RNA was then isolated to measure SDMGC and TRIM16 expression levels using quantitative reverse transcriptase (qRT)-PCR. Statistical analyses including the Mann-Whitney U test and correlation tests were carried out using R v4.5. GraphPad Prism was also used to plot the receiver operating curve (ROC). RESULTS: The results demonstrated the significant overexpression of lncRNAs SDMGC and downregulation of TRIM16 in GC tissues as compared to their corresponding marginal normal tissue samples (P = 0.005 and P = 0.009, respectively). No association with clinicopathological variables was observed for either SDMGC or TRIM16. Moreover, the results demonstrated a small positive correlation between SDMGC and TRIM16. Evaluation of the diagnostic value of SDMGC and TRIM16 showed poor biomarker potency for these genes. CONCLUSION: In conclusion, the results indicated an increase in the expression of SDMGC and a decline in the expression pattern of TRIM16 among the Iranian population. The results indicated a key tumor-accelerative function of SDMGC and a pivotal tumor-suppressing role of TRIM16 in GC patients.

All-trans retinoic acid-mediated miR-30a up-regulation suppresses autophagy and sensitizes gastric cancer cells to cisplatin.

AIMS: The potential of all-trans retinoic acid (ATRA) in regulating some microRNAs (miRNAs) involved in multiple cancer-related pathways, including resistance to chemotherapeutics, may be a valuable idea for overcoming the CDDP resistance of GC cells. MAIN METHODS: Treatment of gastric AGS and MKN-45 cells with CDDP enriched the CDDP surviving cells (CDDP-SCs). The abilities of chemoresistance to CDDP drug, migration, either apoptosis or cell cycle distribution, spheroid body formation and changes at miRNA and protein levels were evaluated in vitro by MTT assay, colony formation assay, flow cytometry, tumor spheres culture, qRT-PCR and western blot assay in CDDP-SCs and ATRA-treated CDDP-SCs cells, respectively. KEY FINDINGS: CDDP-based chemotherapy significantly reduced microRNA-30a (miR-30a) levels in GC cells. We also observed elevated autophagy activity in cancer cells that possess stem cell-like properties with overexpressed specific stem cell markers. Our extended study suggested that the reduction of miR-30a by CDDP treatment, is the possible underlying mechanism of enhanced autophagic activity, as demonstrated by enhancing autophagy-related protein beclin 1 and LC3-II/LC-I ratio. The addition of ATRA in the culture medium of GC cells increased the expression of miR-30a, and disturbed characteristic CSC-like properties. Additional studies revealed that the increased expression of miR-30a declined the expression level of its target gene, beclin 1, and beclin 1-mediated autophagy. This leads to promoted CDDP-induced GC cell apoptosis and G2/M cell cycle arrest. SIGNIFICANCE: Overall, miR-30a/autophagy signaling has a critical role in regulating the chemoresistance of GC cells that ATRA could modulate.

Suppression of lncRNA NORAD may affect cell migration and apoptosis in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is a major malignancy that threatens people's lives worldwide. Long noncoding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) is known to be a potential oncogene in many cancers and may promote cell migration and metastasis, and decrease apoptosis rate. MATERIAL AND METHODS: NORAD expression was measured in 70 pairs of GC tissues and their adjacent normal tissues (ANTs) by quantitative real-time polymerase chain reaction. Si-NORAD gene knockdown study and cellular assays were conducted to assess the correlation between NORAD expression and cell viability, apoptosis, migration, and metastasis. RESULTS: NORAD was significantly overexpressed in GC tissues compared to ANTs (P value < 0.0001). The receiver operating characteristic curve indicated the AUC of 0.721 with the sensitivity and specificity of 78.57 and 61.43, respectively (P value < 0.0001). NORAD downregulation leads to decreased cell viability (P value < 0.001) and migration (P value < 0.01), increased apoptosis rate (P value < 0.0001), and increased protein level for PTEN, E-cadherin, and Bax, but decreased protein level for Bcl-2. CONCLUSION: Generally, NORAD may serve as a potential diagnostic biomarker in GC.

Overexpression of lncRNA DLEU1 in Gastric Cancer Tissues Compared to Adjacent Non-Tumor Tissues.

PURPOSE: Gastric cancer (GC) is caused by environmental factors and genetic changes of protein-coding- and non-coding sequences, which entail short non-coding RNAs (microRNAs) and long non-coding RNAs (lncRNAs). DLEU1 (deleted in lymphocytic leukemia 1), as an effective lncRNA located on chromosome 14.3q 13, modulates the nuclear factor-kB (NF-kB) signaling pathway. This gene usually plays an oncogenic role in the tumorigenesis of multiple types of cancer. The present study examined the expression level of DLEU1 and its association with clinical-pathological characteristics in GC. METHODS: Total RNA of 100 specimens was extracted by TRIzol reagent. After cDNA synthesis, qRT-PCR analysis was performed to measure the expression level of the DLEU1 gene and the obtained data were analyzed by SPSS 16.0. RESULTS: The relative expression level of DLEU1 significantly increased in tumor specimens compared to the normal tumor margin specimens. The biomarker index of lncRNA DLEU1 was 0.7 in tumor tissues. The observed high expression level of DLEU1 was pertinent to the pathological progressive TNM stage, lymph node metastasis, differentiation degree, patient's age and lifestyle, and Helicobacter pylori infection in GC patients. CONCLUSION: The obtained findings suggested that DLEU1 acts as an oncogene in GC and might be a new target for gene therapy of GC.

miR-424: A novel potential therapeutic target and prognostic factor in malignancies.

microRNAs are endogenous, noncoding RNAs. Showing both tumor-suppressive and oncogenic characteristics, miRNAs can regulate important processes in malignancies. This review aimed at highlighting the recent studies on the contribution of miR-424 to the modulation of carcinogenesis and exploring its probable clinical effectiveness in the diagnosis and therapy of malignancies. The data were extracted from all papers published from 2013 until 2020. Mature miR-424 leads to the degradation of its target transcripts or the suppression of translation via binding to the molecular targets. miR-424 is involved in modulating p53, PI3K/Akt, Wnt, and other molecular pathways, thereby regulating cellular growth, apoptosis, differentiation, chemoresistance, and cancer immunity. miR-424 was introduced as a tumor-suppressive miR in numerous types of cancers while as an oncogene in several cancers. Regarding the cancer dependent role of miR-424, it may be a prognostic and diagnostic biomarker and a potential candidate for the treatment of cancers.

Relationships Between IL-13 and IL-4 Genotypes and Aeroallergens with Risk of Allergic Rhinitis in Iranian-Azeri.

Background: Up to 40% of the world populations are affected by allergic rhinitis (AR). Interplay between genetics, epigenetics, and environmental factors leads to allergic disease. Objective: In this study, we evaluated the accompaniment between polymorphic variants of IL-13 and IL-4 and aeroallergens among Iranian-Azeri children and adolescent in AR's risk. Methods: Five-hundred AR patients and 300 healthy individuals were enrolled in this study after diagnosis via blood testing for IgE and skin prick test by subspecialty of Allergy and Immunology from Azerbaijan, northwest of Iran, from 2017 to 2019. Genomic DNA was prepared from all samples for genotyping of IL-4 and IL-13. Results: We identified genetic variation of IL-13 and IL-4 and important aeroallergens that could increase the AR risk during childhood and adolescent. The risk of AR increased in the subjects with +2044GA genotype of IL13 [adjusted odds ratio (OR), 1.80; 95% confidence interval (CI), 0.97-3.33] and -590CT genotype of IL4 (adjusted OR, 1.94; 95% CI, 1.00-3.87) in childhoods, compared with the control subjects. However, none of genotypes and allele frequencies of IL4 -590C/T and IL13 +2044G/A polymorphisms revealed significant variation between the AR patients and controls in adulthood. The frequency of sensitization to pollens was high in all genotypes of IL4 -590C/T and IL13 +2044G/A polymorphisms in both age groups of AR patients. Conclusion: AR is considered to be the most common form of atopic disease. Susceptible individuals had family history of allergic disease and indicated sensitivity to various environmental factors. In this study, pollen and feather played an important role in occurrence of AR. Childhood with GA at IL13 +2044 and CT at IL4 -590 are at increased risk for AR. Moreover, further studies with more samples are required to confirm our findings and also to help us develop new procedure for genetically detecting more efficient proceedings of prevention and intervention.

An update review of deregulated tumor suppressive microRNAs and their contribution in various molecular subtypes of breast cancer.

BACKGROUND: Breast cancer (BC) is histologically classified into hormone-receptor+ (ER+, PR + ), human epidermal growth factor receptor-2+ (Her2 + ), and triple-negative breast cancer (TNBC) types. The important contribution of tumor-suppressive (TS) microRNAs (miRs) in BC development and treatment have been well-acknowledged in the literature. OBJECTIVE: The present review focused on the contribution of recently examined TS miRs in the progression and treatment of various histological subtypes of BC. RESULTS: In summary, various miRs have tumor-suppressive roles in BC, so that their aberrant expression leads to the abnormality in the cellular processes such as enhanced cell growth, decreased apoptosis, cell migration and metastasis, and decreased sensitivity to chemotherapy through deregulated expression of oncogene targets of TS miRs. CONCLUSION: TS miRs could be regarded as a proper molecular target for target therapy of BC. However, further in vitro and in vivo investigations are required to confirm the exact molecular functions of TS miRs in BC cells to offer more efficient targeted therapies.

Disregulation of miR-216a and miR-217 in Gastric Cancer and Their Clinical Significance.

OBJECTIVE: The majority of gastric cancer (GC) diagnoses occur at the middle or late stage of the disease, indicating that finding novel biomarkers that could be detectable at earlier stage is urgently needed. Accumulating studies have shown that microRNAs, a class of tiny single-stranded RNAs, play important roles in multiple biological processes including cancer development. The present study aimed to evaluate the effect of miR-216a and miR-217 in GC. MATERIAL AND METHODS: The real-time quantitative reverse-transcription PCR was exploited to identify and compare the expression levels of miR-216a and miR-217 in 37 pairs of samples of gastric cancer tissue and adjacent normal tissue. Superimposed on this, the potential relationship between miR-216a/217 levels and clinicopathological parameters in patients suffering GC was explored. RESULTS: The results obtained from this study showed that the miR-216a is significantly upregulated in gastric cancer tissues, compared with adjacent normal tissues, but the altered expression of miR-217 was not significant. For miR-216a/217, no significant correlations were detected between expression levels of these miRNAs and clinical and pathological characteristics of patients. CONCLUSION: This prospective study proposes that upregulation of miR-216a might represent an important mechanism for the development of gastric cancer.

Overexpression of SSH1 in gastric adenocarcinoma and its correlation with clinicopathological features.

BACKGROUND: Gastric adenocarcinoma is known to be the fourth most common cancer type and the second cause of cancer-related deaths. Movement and invasion of cancer cells is one of the major characteristics of the cancer phenotype that various types of network regulate this. Expression levels of slingshot diphosphatase 1 (SSH1) gene has been modulated in this pathway. SSH1 acts as a dephosphorylation and activator of cofilin that this regulating and activating by SSH1 can play a major role in the mobility and migration of the cell. The aim of this study was to compare the expression level of SSH1 genes between tumor and corresponding adjacent non tumor gastric tissues and healthy tissue of gastric adenocarcinoma. METHODS: In this study, mRNA of 40 gastric adenocarcinoma and corresponding adjacent non tumor gastric tissues and 15 healthy biopsy samples was extracted, then after cDNA synthesis, real-time polymerase chain reaction was performed to measure gene expression. RESULTS: According to REST analysis, the relative expression of SSH1 was significantly increased in gastric cancer tissues compared to the corresponding adjacent non tumor gastric tissue samples and normal tissue. Nevertheless, the result revealed no substantial correlation between the expression levels of SSH1 with clinical features. The biomarker index for SSH1 was obtained as 0.89. CONCLUSIONS: The results obtained from investigating SSH1 expression are indicative of significant changes in the expression of this gene in gastric adenocarcinoma. This gene can also be used as a biomarker for gastric cancer.

Helicobacter pylori virulence factors in relation to gastrointestinal diseases in Iran.

PURPOSES: Helicobacter pylori as an important pathogenic bacterium that colonizes in gastric mucosa, is one of the causative agents in development of some types of gastric diseases, such as chronic active gastritis, peptic ulcer disease (PUD) and gastric cancer (GC). In this review, the aim is studying different genotypes of H. pylori, and the extent of their participation in the pathogenesis of this bacterium which creates gastroduodenal disorders. RESULTS: Some genotypes of H. pylori have a major role in creation of gastroduodenal diseases, whereas some other genotypes of the bacterium do not cause gastric diseases in Iran. It was also reported that some genotypes of this bacterium in different conditions and among different ethnic groups demonstrate different effectiveness. CONCLUSION: Role of genotypes of H. pylori in creation of gastroduodenal diseases is different among various regions and ethnic groups of Iran.