long non coding rna

Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA types, have emerged as key regulators in neurodegenerative diseases and brain tumors. This review aims to provide insights into the role of ncRNAs in these conditions and their potential as diagnostic and therapeutic targets. We systematically reviewed literature from databases such as PubMed, Scopus, and Web of Science, applying specific inclusion and exclusion criteria to ensure comprehensive coverage of recent advancements. Although ncRNAs are involved in a range of molecular pathways, challenges in clinical translation, including specificity, cost, and validation, persist. This review highlights innovative strategies to overcome these barriers and promote the clinical application of ncRNAs. Moreover, we explore the emerging role of extracellular vesicle-enriched ncRNAs as cell-free therapeutic options for neurodegenerative diseases. The findings presented here emphasize the need for robust validation and the development of specific ncRNA-based treatments.

Functional long non-coding RNAs (lncRNAs) have a significant role in crucial pathways associated with cancer progression. The overexpression of the H19 gene has been documented in various types of cancer. The present study was conducted with aim to assess the correlations between two specific variations of the lncRNA H19 gene (rs217727C>T and rs2839698C>T) with the likelihood of developing ovarian cancer.

This case-control analysis was conducted on a sample of three hundred individuals, comprising 150 cases diagnosed with ovarian cancer and 200 control subjects. The tetra-primer ARMS-PCR method was used to assess the correlation between two single nucleotide polymorphisms (SNPs) of lncRNA H19 and the susceptibility to ovarian cancer.

There was a strong association between the rs2839698 variant and the risk of ovarian cancer. The Co-dominant model of rs2839698 (CT vs. CC) demonstrated a statistically significant risk reduction, with an odds ratio (OR) of 0.45 (CI 0.26-0.78, P = 0.003). Similarly, the dominant model of rs2839698 (CT+TT vs. CC) exhibited a significant decrease in risk, with an OR of 0.54 (CI 0.32-0.91; P = 0.01). Lastly, the Over-dominant model of rs2839698 (CT vs. CC+TT) demonstrated a significant risk reduction, with an OR of 0.50 (CI 0.32-0.77; P = 0.01).

The results of the present study indicate that the rs2839698 variant in lncRNA H19 may influence the vulnerability to ovarian cancer in Iranian population.

Laryngeal squamous cell carcinoma (LSCC) remains a significant global health challenge despite advances in treatment. This study investigated the involvement of LINC01980, a long non-coding RNA, in LSCC pathogenesis. We conducted an integrative analysis of transcriptomic data sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases to identify genes that are differentially expressed in LSCC. LINC01980 expression was evaluated in 32 matched pairs of advanced-stage LSCC and adjacent normal tissues using quantitative real-time PCR (qRT-PCR). The potential competing endogenous RNA (ceRNA) network involving LINC01980 was explored through bioinformatics analyses. Findings revealed significant upregulation of LINC01980 in LSCC tissues compared to normal adjacent tissues (p < 0.0001), with elevated expression in 78.125% of tumor samples. Receiver Operating Characteristic (ROC) curve analysis demonstrated LINC01980's potential as a diagnostic biomarker (AUC = 0.7666, p = 0.0002). While no significant correlations were found between LINC01980 expression and clinicopathological features, bioinformatics analyses identified potential LINC01980/ miRNA/ mRNA regulatory network involving hsa-let-7e-5p and hub gene MMP9. This study provides insights into LINC01980's role in LSCC and suggests its potential as a diagnostic biomarker and therapeutic target. Further research is warranted to elucidate the precise molecular mechanisms of LINC01980 in LSCC progression.

Long non-coding ribonucleic acids (lncRNAs) have been implicated as possible circulating stroke indicators. This study focused on the expression status of antisense non-coding ribonucleic acid in the INK4 locus (ANRIL) and myocardial infarction associated transcript (MIAT) in patients with cerebral venous thrombosis (CVT). In this study, fifty patients with CVT and one hundred age/gender-matched individuals as controls were included. The circulating levels of ANRIL and MIAT in the first 24 hours after admission were evaluated using the quantitative real-time polymerase chain reaction (RT-PCR) method. We compared the expression levels of ANRIL and MIAT between patients and controls using the independent two-sample t-test. Subgroup analysis was used to investigate the association of lncRNAs with clinical characteristics in patients with CVT. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the diagnostic value of two lncRNAs in patient assessment. The relative expression of lncRNAs ANRIL and MIAT significantly decreased in patients compared to the control. ANRIL and MIAT were shown as potential markers for discriminating patients with CVT from the healthy controls with an area under the curve (AUC) of 0.98 and 0.99, respectively. For the first time, we found down-regulation and diagnostic potential of lncRNAs-ANRIL and MIAT in the blood of patients with CVT.

Diabetes mellitus type 2 (T2DM) is a chronic condition characterized by insulin resistance, affecting approximately 530 million adults globally, with a prevalence of 10.5% among individuals aged 20 to 79. In Iraq, the prevalence is significantly higher at 13.9%.

This study examines the relationship between long noncoding RNA HOX transcript antisense RNA (HOTAIR) polymorphisms and T2DM risk, investigating HOTAIR's potential as a diagnostic marker.

Blood samples were collected from 28 T2DM patients and 20 healthy controls, with physiological parameters measured. HOTAIR plasma levels were assessed using quantitative real-time (qRT)-PCR, and single-nucleotide polymorphisms rs12826786 and rs1899663 were analyzed through amplification refractory mutation system (ARMS)-PCR.

HOX transcript antisense RNA expression was found to be 6.6 times higher in T2DM patients compared to controls, suggesting its involvement in T2DM pathophysiology. Genotype distributions adhered to Hardy-Weinberg equilibrium, with the rs12826786 C allele appearing protective against T2DM, while rs1899663 showed no significant association. Statistical analysis identified a significant relationship between the rs12826786 genotype and body mass index (BMI), though other diabetes-related metrics did not show significant results.

The findings suggest that elevated HOTAIR expression may play a role in T2DM, highlighting the need for further investigation into these associations and their potential implications for diagnosis and risk assessment.

Oral Squamous Cell Carcinoma (OSCC) is a pressing global health challenge. Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators. Among these, the lncRNA ANRIL (antisense non-coding RNA in the INK4 locus) has a role in cancer progression. The aim of this study was to look into possible links between a certain genetic variant of lncRNA ANRIL, rs10757278 A/G, and OSCC risk and tumor features in the Iranian population.

We conducted a case-control study, enrolling 101 OSCC patients and 115 healthy controls. We took out the genomic DNA and used the tetra-primer ARMS-PCR (tetra-primer amplification refractory mutation system-polymerase chain reaction) method to find the rs10757278 genotype. We evaluated the associations between genotypes and both OSCC susceptibility and various tumor characteristics.

Although we did not observe significant differences in allele and genotype frequencies between cases and controls, we revealed compelling associations between genotypes and tumor characteristics. Genotypes AG and GG were linked to smaller tumor sizes, while genotypes with at least one wild-type allele (A) were linked to well differentiated OSCC. Specific genotypes exhibited significant associations with tumor sites, with the tongue demonstrating the strongest correlation.

The rs10757278 A/G variant did not show a direct link with OSCC risk, but its complex effect on tumor behavior suggests that it may play a bigger role in the development of OSCC. These findings open avenues for future investigations to uncover hidden genetic interactions, and potentially inform more targeted therapeutic strategies.

 Circular RNAs (Circ RNA) are a large class of non-coding RNAs which particularlystable RNAs and mostly originate from gene exons in animals. circRNAs are extremely abundantin the mammalian brains. They play role in the biological function and development of neurons.Nrf2 (nuclear factor erythroid 2–related factor 2) is a transcription factor that regulates cellularantioxidants and improves hippocampal synaptic plasticity, learning and memory. The aim ofthis study is the evaluation of Nrf2’s circRNA expression in the hippocampus of rats duringoxidative stress and the prediction of their function by bioinformatic tools.

 After evaluation of Nrf2’s circRNA prediction from circAtlas by BLAST, 3 out of 4sequences with high homology were selected and circ-Nrf2s expression was evaluated by qPCR,the interaction with micro RNAs and proteins was evaluated by miRDB, TargetScan, catRAPIDand HDOCK web server. Except control group, two groups of rats were treated with H2O2 (1%and 5%) then rats were sacrificed and hippocampal tissue was separated. qPCR was performedfor Nrf2 pathway gene expression and Nrf2 circRNAs. Then Circ-Nrf2-miRNA and 2circ-Nrf2-protein interaction were evaluated.

 The most important circRNA that origin from Nrf2 is circ-Nrf2-1. Circ-Nrf2-1downregulates in oxidative stress and upregulates in 5% of H2O2 compared to 1%. However,linear Nrf2 was upregulated in both 1% and 5% H2O2. Circ-Nrf2-1 can bind to several miRNAsincluding miR-144-3p, miR-148a-5p, miR-155-5p. It also interacts with Celf1 which plays a rolein oxidative stress.

 According to results, it is plausible to suggest that circNrf2 may play a regulatoryrole in modulating oxidative stress.

The lncRNAs has been linked to several malignancies, including breast cancer. Our objective was to investigate the impact of urothelial carcinoma associated 1 (UCA1) on cellular growth and death by a CRISPR/Cas9 knockdown technique.

In 2020, the CHOPCHOP program was utilized to design two sgRNAs targeting the UCA gene. sgRNA1 and sgRNA2 were inserted into two different CRISPR plasmids to produce two recombinant plasmids. These recombinant plasmids were simultaneously transfected into MCF-7 and MDA-MB 231 carcinoma of the breast cells. Proliferation and apoptosis were compared using the MTT test, CCK-8 assay, and flow cytometry evaluation. RNA-hybrid software, quantitative reverse transcription PCR, and luciferase assays were utilized to confirm the relationship between UCA1 and miR-143.

Proliferated cells were less active in MTT and CCK-8 tests and fellow cytometry analysis. The PX459-sgRNA1,2 group had elevated levels of the cancer biomarker Caspase-3 gene expression (P<0.001). When WT-UCA1 and miR-143 were co-transfected, the luciferase activity was drastically decreased.

One very effective method of regulating cellular proliferation in vitro is the deletion of UCA1, which CRISPR/Cas9 accomplishes.

Recent studies have implicated dysregulated long non-coding RNA (lncRNA) levels in the pathogenesis of type 2 diabetes (T2D). This study aimed to assess the expression of circulating HOTAIR and uc.48+, examining their correlation with clinical and biochemical variables in T2D patients, pre-diabetic individuals, and healthy controls.

Peripheral blood levels of lncRNAs were quantified using QRT-PCR in 65 T2D patients, 63 pre-diabetic individuals, and 63 healthy subjects. Pathway enrichment analysis was conducted to explore the functional enrichment of lncRNA-miRNA targets.

Analysis revealed a significantly elevated circulating level of HOTAIR in both T2D (P < 0.0001) and pre-diabetic patients (P = 0.04) compared to controls. ROC analysis demonstrated that, at a cutoff value of 9.1, with a sensitivity of 80% and specificity of 62%, HOTAIR could distinguish T2D patients from controls (AUC = 0.723, 95% CI 0.637-0.799, P < 0.0001). Spearman correlation analysis identified a significant positive correlation between HOTAIR expression, HbA1c, and insulin resistance (P < 0.005). MiRNA enrichment analysis indicated significant enrichment of diabetes-related pathways among HOTAIR's miRNA targets. Conversely, no significant difference in uc.48+ circulating levels between groups was observed, but a significant positive correlation emerged between uc.48+ and systolic blood pressure.

This study provides evidence that elevated HOTAIR expression levels are associated with T2D progression, suggesting their potential as biomarkers for early diagnosis and prognosis.

Genetic aspects can play an essential role in the occurrence and development of ischemic stroke (IS).Rs1894720 polymorphism is one of the eight single nucleotide polymorphisms (SNPs) in the long non-coding RNA(lncRNA) myocardial infarction-associated transcript (MIAT) locus. The aim of study is the lncRNA MIAT rs1894720polymorphism decreases IS risk by reducing lncRNA MIAT expression.

In this case-control study, we studied 232 Iranian patients and 232 controls. The blood sampleswere collected from patients admitted at different times after stroke symptoms. We enrolled 80, 78, and 74 patientswho arrived at the hospital between 0-24, 24-48, and 48-72 hours after the first appearance of symptoms, respectively.DNA genotyping was done by the tetra-primer ARMS-PCR method. Circulating MIAT levels were evaluated by real-timepolymerase chain reaction (PCR).

The GT genotype of MIAT rs1894720 showed a significant association with the risk of IS (OR=3.53, 95%CI=2.13-5.84, P<0.001). MIAT expression was higher relative to the control within the first hours after IS. The MIATlevels in IS patients with rs1894720 (GT) were significantly lower relative to patients who had the GG and TT genotypes.Linear regression model indicated a significant correlation between MIAT expression with atherosclerotic risk factorsand types of stroke in IS patients. Receiver operating characteristic (ROC) curve analysis showed that the level oflncRNA MIAT after IS could be diagnostic with an area under the curve (AUC) of 0.82. The sensitivity and specificitywere 80.17 and 67.24%, respectively (P<0.001).

Our study demonstrated that the MIAT rs1894720 polymorphism (GT) might increase the risk of IS in theIranian population. MIAT expression was up-regulated in our IS patients. Hence, it could be a diagnostic biomarker for IS.

Scientific research over the past decades has proven the pivotal role of long non-coding RNAs (LncRNAs) in regulating gene expression. The immune responses are controlled through the interaction of pro-inflammatory (predominance of T helper 17 cells (Th17)) and anti-inflammatory cytokines excretion (predominance of Regulatory T cells (Treg)). Recent studies have marked the impact of many diverse LncRNAs on Treg/Th17 imbalances. Moreover, some of the roots and causes of human diseases can be associated with the alterations in the Th17/Treg ratio. In this review study, we overviewed the association between LncRNAs and Th17/Treg, with the potential of providing novel prognostic and diagnostic biomarkers and promising therapeutic targets in various diseases, particularly cancer.

Polycystic ovary syndrome (PCOS), the primary cause of anovulatory infertility in women, may change the gene expression profile of cumulus cells. In human ART (assisted reproductive technology), gene expression profiling in cumulus cells, a non-invasive method, may be used to identify the most competent oocytes. We aim to identify key genes according to the network-based data and assess the suitability of these genes as markers to predict oocyte competence and PCOS diagnosis. The GSE34526 microarray dataset was obtained from the Gene Expression Omnibus (GEO) database. The function and pathway enrichment analysis for DEGs were analyzed. A protein-protein interaction (PPI) network analysis and candidate gene screening were conducted. A two-layer network consisting of mRNA and lncRNA was constructed. Expression levels of hub genes were verified using quantitative RT-PCR (qRT-PCR). A total of 2721 DEGs were retained. The PPI network of selected genes associated with the biological process of “cell communication” was analyzed, and the first 10 key genes were determined by degree. Additionally, 2 hub genes and 2 hub lncRNAs, including STAT3, RHOA, GAS5, and LINC01116, were selected from the lncRNA-mRNA network. Finally, expression levels of STAT3, RHOA, GAS5, and LINC01116 were significantly increased in the cumulus cells of PCOS patients compared to the control group (P<0.05). However, there was no significant difference in expression between the pregnant and non-pregnant groups. STAT3, RHOA, GAS5, and LINC01116 may serve as possible diagnostic markers for PCOS. However, further studies on a larger population are needed to validate this finding.

Context: 

Long non-coding RNA (lncRNA) is a novel set of non-coding RNAs (ncRNA), over 200 nucleotides in length, accounting for the regulation of genes and chromosome structure. There are a few articles, mostly focusing on changes in the expression profile of DANCR. However, this review tried to collect documents to discuss the molecular mechanisms of this lncRNA in different cellular signaling pathways, considering microRNAs, to obtain a better understanding of its mode of action.

Evidence Acquisition: 

Differentiation antagonizing non-protein coding RNA (DANCR) is a cancer-associated lncRNA whose dysregulation, mostly upregulation, has been reported in almost all cancers, particularly in stages of invasion, migration, and progression. The regulatory mechanism of DANCR is mostly working as competitive endogenous RNAs (ceRNAs), leading to the hypothesis that lncRNA DANCR has oncogenic functions in malignancies. LncRNA DANCR harbors a number of MicroRNA Response Elements (MREs) for various microRNAs involved in different pathways, which are responsible for turning the situation toward supremacy for the dissemination of cancerous cells and ultimately metastasis, such as PI3K/Akt, TGF-β, Wnt, JAK-STAT, EMT, and DNA damages. In fact, lncRNA DANCR could potentially sequester microRNAs from their targeted mRNAs, which share the same MREs as DANCR.

This review article provides proper evidence, of why the aberrant expression of DANCR pathophysiologically turns the circumstances toward supremacy for the progression, migration, and invasion of cancerous cells, and proposes this lncRNA as a potent and extremely promising prognostic marker for the early detection of tumor progression and metastasis, as well as a therapeutic target for controlling the progression of several human malignancies.

 Gastric cancer is one of the most prevalent human malignancy-related death worldwide, which is usually diagnosed at the advanced stages resulting in metastasis. Recent studies have revealed that long non-coding RNAs (lncRNAs), which are known as non-coding RNAs, play a significant role in creating variety of molecular pathways (e.g., growth, proliferation, differentiation, and apoptosis) and negatively contribute to many unusual processes, including human cancers. The HOX antisense intergenic RNA (HOTAIR) is one of the novel non-coding RNAs which has recently emerged as a promoter of metastasis in different types of human cancers through epithelial-to-mesenchymal transition (EMT) process. Epithelial-to-mesenchymal transition (EMT) is a cellular process where an epithelial cell could change its phenotype to mesenchymal condition, which plays a crucial role in promoting cell invasion, angiogenesis, and metastases.

 This study aimed to explore the effect of HOTAIR gene silencing on the expression levels of two main markers of EMT signaling pathway, fibronectin (FN1) and claudin4 (CLDN4) in MKN45 cellular model of gastric cancer. The MKN45 cells were subjected to HOTAIR specific siRNA for 48 hours, and the extracted RNAs were subjected to cDNA synthesis and real-time PCR. The expression change was calculated using 2-ΔΔct.

 Our findings showed that FN1 and CLDN4 were upregulated in MKN45 cells. Following the transfection of cell by HOTAIR siRNA, both FN1 and CLDN4 genes were significantly downregulated.

 HOTAIR long non-coding RNA may have regulated the expression levels of FN1 and CLDN4 genes in EMT signaling pathway. However, it was recommended that further experimental analyses should be carried out to confirm this observation. In other word, our study result may not have been applied as a therapeutic access until additional experiments were conducted.

Long non-coding RNAs (lncRNAs) feature prominently in tumors. Reportedly, lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) is aberrantly expressed in a variety of tumors. The present study was aimed to explore ZEB2-AS1 functions and determine mechanism in hepatocellular carcinoma(HCC) progression. In this experimental study, expressions of ZEB2-AS1, microRNA (miR)-582-5p and forkhead box C1 (FOXC1) mRNA in HCC tissues and cell lines were detected via quantitative reveres transcription polymerase chain reaction (qRT-PCR). After establishing gain- and loss-of-functions models, cell counting kit-8, 5-bromo-2’-deoxyuridine (BrdU), Transwell assays and flow cytometry analysis were conducted to examine HCC cell multiplication, migration, invasion and apoptosis, respectively. The targeted relationship between miR-582-5p and ZEB2-AS1 was verified via dual-luciferase reporter gene assay. Western blot was utilized for detecting FOXC1 expression in HCC cells after selectively regulating ZEB2-AS1 and miR-582-5p. In HCC tissues and cells, ZEB2-AS1 expression was increased. High ZEB2-AS1 expression was related to relatively large tumor volume, increased tumor-node-metastasis (TNM) stage and positive lymph node metastasis of the patients. ZEB2-AS1 overexpression facilitated HCC cell multiplication, migration, invasion and suppressed apoptosis, while ZEB2-AS1 knock-down caused the opposite effects. It was also confirmed that ZEB2-AS1 could competitively bind with miR-582-5p to repress its expression, and indirectly up-regulate FOXC1 expression level in HCC cells. The current study revealed that ZEB2-AS1 was over-expressed in HCC tissues and cells. It also upregulated FOXC1, through sponging miR-582-5p, to promote HCC progression. This provides new perspectives for elucidating the pathogenesis of HCC.

Lung cancer is the second most common cancer and has high morbidity and mortality worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of the cases. Over-expression of epidermal growth factor receptor (EGFR) has been clarified in different cancers, and has been shown to have a crucial role in tumor progression. In this study, we evaluated long non-coding RNA small NF90-associated RNA (snaR) expression in different EGFR-statue cell lines. Knockdown experiments were conducted to analyze snaR expression in selected cell lines. MTT and transwell assays were respectively employed to evaluate the proliferative and invasive abilities of NSCLC cells. The expression of snaR was remarkably up-regulated in SPC-A1 and A549 wild-type EGFR cell lines. Down regulation of snaR with small interfering RNA significantly inhibited cell invasion as well as proliferation of SPC-A1 and A549 cells. Our results indicate that snaR may be a potential therapeutic biomarker for NSCLC.

Breast cancer, is one of most frequent cancers across women, is recognized as a diverse and difficult disease that continues to be a serious public health problem. Long non-coding RNAs have already attracted a lot of interest as a result of the advancement of next-generation sequencing methods. Various studies indicate that long non-coding RNAs play an essential part in tumor growth. Even though the biological purpose and molecular processes of long non-coding RNAs are still unknown, modern data has shown that a variety of long non-coding RNAs express inappropriately in malignancies, particularly breast cancer. This review highlighted the most recent research on long non-coding RNAs in breast cancer, with an emphasis on the many molecular functions of regulatory long non-coding RNAs.

Acute lymphoblastic leukemia (ALL) is a fetal hematologic disorder that is mostly observed in children. Both B and T lymphocytes have been reported to play a role in ALL etiology. Long non-coding RNAs (lncRNAs) are large regulatory molecules with more than 200 nucleotides that participate in various cellular processes. Methylation at the promoter regions of these regulatory molecules has been reported to vary between ALL patients and healthy controls. This study aimed to evaluate methylation status at promoter regions of lncRNAs between these two groups.

In the current study, 80 ALL patients and 80 healthy controls were enrolled. The intravenous blood samples were obtained from all patients and controls. The extracted DNA from blood samples underwent sodium bisulfite treatment. Thereafter, methylation levels in the promoter regions of lncRNAs RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were evaluated using methylation specific-high resolution melting (MS-HRM). Moreover, the receiver operating characteristic curve (ROC) analysis was performed to examine the sensitivity and specificity of the tests.

The methylation levels of all studied lncRNAs including RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were significantly increased (p<0.05). ROC curve analysis also showed that all lncRNAs could be used as diagnostic markers.

This study showed that methylation alterations of lncRNAs could be considered as novel biomarkers for early detection of ALL. Furthermore, owing to the possible role of studied lncRNAs as tumor suppressors, they could be reliable treatment targets for methylation modifications. Further research is still required to elucidate the role of these lncRNAs in ALL etiology.

Colorectal Cancer (CRC) is the third most common cancer in Iranian men and the fourth most common cancer in women. Recent studies have shown that lncRNAs may also engage in remodeling the tumor microenvironment and tumor metastasis. A lncRNA called LBX2 antisense RNA 1 (LBX2-AS1) has been reported to exert crucial regulatory actions in various cancer. In this study, we evaluate the expression of LBX2-AS1gene in 30 colorectal cancer tumor samples. Gene expression was assessed by Real-time PCR method and the results were analyzed by 2^-DDct. relative expression of this gene in tumor samples compared to healthy samples showed a 1.4-fold increase in tumor samples. According to our findings in this study and the results of other studies, it can be concluded that this gene can be used as a therapeutic target.