Association of ANRIL Gene Polymorphisms with Gastric Cancer Risk: A Case-Control Study.

Background: Gastric cancer's (GC) cause is unknown, but its complexity indicates that, in addition to environmental factors, it may have genetic origins. Scientists are studying single-nucleotide polymorphisms (SNPs) in the antisense noncoding RNA in the INK4 locus (ANRIL) gene, which encodes a long noncoding RNA molecule. They found a link between the ANRIL gene product and some polymorphisms and GC, suggesting genetic changes may lead to precancerous conditions. Methods: In a case-control research that included 250 patients with GC and 210 controls who were age- and gender-matched, four SNPs within the ANRIL gene were genotyped. These SNPs were rs1333049, rs496892, rs2383207, and rs2151280. Tetra-primer amplification refractory mutation system-PCR was utilized to carry out the process of genotyping. Results: It was found that the chance of developing GC was connected with three SNPs rs2151280, rs1333049, and rs496892. Nevertheless, rs2383207 did not demonstrate any meaningful connection. In addition, whereas CCTC and TTCC haplotypes were shown to be less common, certain haplotypes that contained these SNPs (TTCG, TCTC, and TTTC) displayed a considerably higher prevalence in the cancer group in comparison to the control group. Conclusion: This study showed novel associations between specific ANRIL gene polymorphisms (SNPs) and the risk of GC. These findings shed light on the potential role of ANRIL SNPs in GC risk and highlight the need for additional research to clarify the underlying functional processes. Understanding these functional processes might lead to developing novel diagnostic or treatment approaches for this cancer.

Transcription of biological aging markers (ANRIL, P16INK4a, TBX2, and TERRA) and their correlations with severity of sulfur mustard exposure in veterans.

Sulfur mustard (SM) exposure has delayed harmful effects, including premature biological aging. This study aimed to evaluate the expression of aging markers (i.e., ANRIL, P16INK4a, TBX2, and TERRA) and assess their correlation with the severity of SM exposure in the long term. The study was conducted on two volunteer groups. 1) SM-exposed group, exposed to SM once in 1987 during the war; divided into three subgroups based on the injury severity, asymptomatic (without any clinical signs), mild, and severe; 2) Non-exposed group. In the SM-exposed group, ANRIL transcript was decreased, especially in subgroups of mild and severe. TBX2 transcript was also decreased in the total SM-exposed group. This decrease was more significant in the mild and severe subgroups than in asymptomatic ones. P16INK4a transcript was increased in the SM-exposed group, especially in the asymptomatic subgroup. The increase in TERRA transcript was also significant in all subgroups. There was a positive correlation between the TERRA transcript and the severity of injury, while this correlation was negative for the ANRIL. It is concluded that the delayed toxicity of SM may be associated with dysregulation of aging markers leading to premature cellular aging. These markers' alterations differed according to the severity of SM injury.

Deletion of the Murine Ortholog of the Human 9p21.3 Locus Leads to Insulin Resistance and Obesity in Hypercholesterolemic Mice.

The 9p21.3 genomic locus is a hot spot for disease-associated single-nucleotide polymorphisms (SNPs), and its strongest associations are with coronary artery disease (CAD). The disease-associated SNPs are located within the sequence of a long noncoding RNA ANRIL, which potentially contributes to atherogenesis by regulating vascular cell stress and proliferation, but also affects pancreatic ß-cell proliferation. Altered expression of a neighboring gene, CDKN2B, has been also recognized to correlate with obesity and hepatic steatosis in people carrying the risk SNPs. In the present study, we investigated the impact of 9p21.3 on obesity accompanied by hyperlipidemia in mice carrying a deletion of the murine ortholog for the 9p21.3 (Chr4Δ70/Δ70) risk locus in hyperlipidemic Ldlr-/-ApoB100/100 background. The Chr4Δ70/Δ70 mice showed decreased mRNA expression of insulin receptors in white adipose tissue already at a young age, which developed into insulin resistance and obesity by aging. In addition, the Sirt1-Ppargc1a-Ucp2 pathway was downregulated together with the expression of Cdkn2b, specifically in the white adipose tissue in Chr4Δ70/Δ70 mice. These results suggest that the 9p21.3 locus, ANRIL lncRNA, and their murine orthologues may regulate the key energy metabolism pathways in a white adipose tissue-specific manner in the presence of hypercholesterolemia, thus contributing to the pathogenesis of metabolic syndrome.

Potential Links between ANRIL and MiRNAs in Various Cancers.

Non-coding RNAs are mainly divided into two categories, one is small non-coding RNA represented by miRNA, and the other is long non-coding RNA longer than 200 bp. Further studies on non-coding RNAs have revealed that long non-coding RNAs not only have carcinogenic effects, but also have potential links with miRNAs. Antisense non-coding RNA in the INK4 locus (ANRIL/CDKN2B-AS1), one of the five subtypes of long non-coding RNA, has been proved to play a role of oncogene in many cancers, such as gastric cancer, cervical cancer, prostate cancer and non-small cell lung cancer. Knockdown ANRIL can significantly inhibit the proliferation and migration of cancer cells, while also negatively regulating the expression of related miRNAs. This suggests that ANRIL may serve as a potential target for the development of drugs that provide new strategies to improve the effectiveness of cancer treatment. In our review, we summarize the current association between ANRIL and miRNAs in various cancers.

ANRIL: A Long Noncoding RNA in Age-related Diseases.

The intensification of the aging population is often accompanied by an increase in agerelated diseases, which impair the quality of life of the elderly. The characteristic feature of aging is progressive physiological decline, which is the largest cause of human pathology and death worldwide. However, natural aging interacts in exceptionally complex ways within and between organs, but its underlying mechanisms are still poorly understood. Long non-coding RNA (lncRNA) is a type of noncoding RNA that exceeds 200 nucleotides in length and does not possess protein-coding ability. It plays a crucial role in the occurrence and development of diseases. ANRIL, also known as CDKN2B-AS1, is an antisense ncRNA located at the INK4 site. It can play a crucial role in agerelated disease progression by regulating single nucleotide polymorphism, histone modifications, or post-transcriptional modifications (such as RNA stability and microRNA), such as cardiovascular disease, diabetes, tumor, arthritis, and osteoporosis. Therefore, a deeper understanding of the molecular mechanisms of lncRNA ANRIL in age-related diseases will help provide new diagnostic and therapeutic targets for clinical practice.

lncRNA Biomarkers of Glioblastoma Multiforme.

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

Genetic variants of ANRIL and coronary artery disease: Insights from a Turkish study population.

BACKGROUND AND AIM: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality globally despite advancements in treatment. Long non-coding RNAs (lncRNAs) play crucial roles in the atherosclerotic process, with ANRIL being one such lncRNA. This study explored the association between ANRIL polymorphisms (rs1333049:C > G, rs564398:T > C, and rs10757274:A > G) and CAD along with CAD risk factors in a Turkish patient group. METHODS: The study included 1285 participants, consisting of 736 patients diagnosed with CAD (mean age = 63.3 ± 10.5 years) and 549 non-CAD controls (mean age = 57.52 ± 11.01 years). Genotypes for rs1333049, rs564398, and rs10757274 were determined using qRT-PCR. RESULTS: G allele carriage of both rs1333049 and rs10757274 polymorphisms were associated with higher Gensini score, SYNTAX score, total cholesterol, and triglyceride levels in female CAD patients and non-CAD males. Females with rs564398 CC genotype were more susceptible to CAD (p = 0.02) and severe CAD (p = 0.05). Moreover, the G and T alleles of rs10757274 and rs564398 were more prevalent among hypertensive males. Also, carrying the C allele for rs564398 was associated with a decreased risk for type 2 diabetes mellitus (T2DM) (p = 0.02). Besides, carriers of the rs1333049 C allele for decreased risk for T2DM (p = 0.03) and CAD complexed with T2DM (p = 0.04) in logistic regression analyses. CONCLUSIONS: In conclusion, selected ANRIL polymorphisms were associated with CAD presence/severity and CAD risk factors, T2DM, and hypertension. Notably, this study, the largest sample-sized study examining the effects of selected polymorphisms on CAD and its risk factors among Turkish individuals, supported the findings of previous studies conducted on different ethnicities.

The effects of ANRIL polymorphisms on colorectal cancer, tumor stage, and tumor grade among Iranian population.

BACKGROUND: Colorectal cancer (CRC) is a type of neoplasm, developing in the colon or rectum. The exact etiology of CRC is not well known, but the role of genetic, epigenetic, and environmental factors are established in its pathogenesis. Therefore, the aim of this research was to explore the effects of ANRIL polymorphisms on the CRC and its clinical findings. METHODS AND RESULTS: The peripheral blood specimens were collected from 142 CRC patients and 225 controls referred to Milad Hospital, Tehran, Iran. PCR- RFLP method was used to analyze ANRIL rs1333040, rs10757274 rs4977574, and rs1333048 polymorphisms. The ANRIL rs1333040 polymorphism was related to a higher risk of CRC in the co-dominant, dominant, and log-additive models. ANRIL rs10757274, rs4977574, and rs1333048 polymorphisms showed no effect on CRC susceptibility. The CGAA and TGGA haplotypes of ANRIL rs1333040/ rs10757274/ rs4977574/rs1333048 polymorphisms were associated with the higher and the lower risk of CRC respectively. The rs1333040 polymorphism was associated with higher TNM stages (III and IV). The frequency of ANRIL rs10757274 polymorphism was lower in CRC patients over 50 years of age only in the dominant model. In addition, the rs10757274 was associated with well differentiation in CRC patients. CONCLUSION: The ANRIL rs1333040 polymorphism was associated with a higher risk of CRC and higher TNM stages. ANRIL rs10757274 polymorphism was associated with the well-differentiated tumor in CRC.

Single-cell sequencing analysis confirms the association of ANRIL with the increased smooth muscle cell proliferation and migration gene signatures in pulmonary artery hypertension in silico.

PURPOSE: Smooth muscle cell (SMC) dysregulation is part of the pathological basis of pulmonary artery hypertension (PAH). We aimed to explore the heterogeneity of SMCs in PAH. METHODS: The profile GSE210248 was obtained from NCBI Gene Expression Omnibus, containing the scRNA-seq data of pulmonary arteries (PA) from three patients with PAH and three healthy donors. After quality control, normalization, and dimension reduction, cell clustering analysis was performed. Differential expression analysis and functional enrichment analysis were carried out successively in smooth muscle cells (SMCs). The enrichment scores of cell cycle and cell migration gene sets in SMCs were calculated. Then, the Spearman correlation coefficients between antisense non-coding RNA in the INK4 locus (ANRIL) expression and two gene sets were computed. RESULTS: Eight cell clusters were identified in PA from samples. The proportion of SMCs was increased in PAH samples. SMCs were divided into five subclusters with diverse biological functions. Muscle contraction-related SMC1 was decreased, while extracellular matrix organization-related SMC2, immune and inflammatory response-related SMC4 and SMC5 were increased in PAH samples compared with healthy donors. The enrichment scores of cell cycle and cell migration gene sets in SMCs were higher in PAH samples than in donors. ANRIL was down-regulated significantly in PAH samples and was negatively related to the scores of two gene sets. CONCLUSION: SMCs exhibited significant heterogeneity in PAH. The altered abilities of SMC proliferation and migration in PAH were associated with ANRIL expression.

LncRNA ANRIL Promotes Glucose Metabolism and Proliferation of Colon Cancer in a High-Glucose Environment and is Associated with Worse Outcome in Diabetic Colon Cancer Patients.

BACKGROUND: The potential involvement of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC) has been previously reported. Epigenetic changes, such as deregulation of long non-coding RNA (lncRNA) and microRNA (miR), have been linked to the advancement of CC; however, the effects of high glucose levels on their deregulation and, in turn, colon cancer remain unexplored. METHODS: Fifty patients had a dual diagnosis of CC and T2DM, and 60 patients with CC without diabetes mellitus were included in the study. qRT-PCR was used to examine the expression of lncRNA ANRIL and miR-186-5p in tissue samples. ANRIL, miR-186-5p, and their downstream target genes HIF-1α, PFK, HK, Bcl-2, and Bax were also determined in CC cell lines under various glucose conditions. Glucose uptake, lactate production and cells proliferation were estimated in CC cell lines. RESULTS: A significant upregulation of ANRIL expression levels (p<0.001) and a significant downregulation of miR-186-5p expression (p<0.001) in diabetic colon cancer specimens compared to those in non-diabetic colon cancer group were observed. MiR-186-5p expression levels were inversely correlated with ANRIL expression levels, blood glucose levels and HbA1c%. Concerning in vitro model, a significant upregulation of ANRIL, downregulation of miR-186-5p, upregulation of HIF-1α, glycolytic enzymes and activation of antiapoptotic pathway was detected in higher glucose concentrations than lower one. There was a significant increase of glucose uptake, lactate accumulation and proliferation of the Caco2 and SW620 cell lines in a dose dependent manner of glucose concentrations. Moreover, a significant positive correlation between glucose uptake and ANRIL expression was shown. CONCLUSIONS: A high-glucose environment can increase the tumor-promoting effect of ANRIL. ANRIL can promote glucose metabolism and colon cancer proliferation by downregulating miR-186-5p with subsequent upregulation of glycolysis enzymes expression and inhibition of apoptosis.

Long Non-coding RNA ANRIL and Its Role in the Development of Age-Related Diseases.

ANRIL is known as a lncRNA that has many linear and circular isoforms and its polymorphisms are observed to be associated with the pathogenesis of many diseases including age-related diseases. Age-related diseases including atherosclerosis, ischemic heart disease, and Alzheimer's and Parkinson's disease are the most common cause of mortality in both developed and undeveloped countries and that is why a better understanding of their pathogenesis and underlying mechanisms is necessary for controlling their healthcare burden.In this review, we aim to gather the data of researches which have investigated the role of ANRIL in aging and its related diseases. The conclusions of this paper might give a new insight for decreasing the mortality rate of these diseases.

Association of long non-coding RNAs and ABO blood groups with acute lymphoblastic leukemia in Egyptian children.

Acute lymphoblastic leukemia (ALL) is the most prevailing cancer among children. Despite extensive studies, ALL etiology is still an unsolved puzzle. Long non-coding RNAs (lncRNAs) emerged as key mediators in cancer etiology. Several lncRNAs are dysregulated in ALL, leading to oncogenic or tumor-suppressive activities. Additionally, a relation between ABO blood groups and hematological malignancies was proposed. The current study intended to explore the association of lncRNAs, ANRIL and LINC-PINT, and their downstream targets, CDKN2A and heme oxygenase-1 (HMOX1), with the incidence of ALL and treatment response, and to determine the distribution of blood groups across different childhood ALL phenotypes. Blood samples were taken from 66 ALL patients (at diagnosis and at the end of remission induction phase) and 39 healthy children. Whole blood was used for blood group typing. Expression of ANRIL, LINC-PINT and CDKN2A was analyzed in plasma by qRT-PCR. Serum HMOX1 was measured using ELISA. ANRIL and CDKN2A were upregulated, while LINC-PINT and HMOX1 were downregulated in newly diagnosed patients. All of which showed remarkable diagnostic performance, where HMOX1 was superior. HMOX1 was independent predictor of ALL as well. LINC-PINT and HMOX1 were significantly upregulated after treatment. Notably, ANRIL and LINC-PINT were associated with poor outcome. No significant difference in the distribution of ABO blood groups was observed between patients and controls. In conclusion, our results suggested an association of ANRIL and LINC-PINT with childhood ALL predisposition, at least in part, through altering CDKN2A and HMOX1 production. Furthermore, the impact of remission induction treatment was newly revealed.

Alternative splicing-related long noncoding RNA ANRIL facilitates hepatocellular carcinoma by targeting the miR-199a-5p/SRSF1 axis and impacting Anillin.

Hepatocellular carcinoma (HCC) is characterized by aberrant alternative splicing (AS), which plays an important part in the pathological process of this disease. However, available reports about genes and mechanisms involved in AS process are limited. Our previous research has identified ANRIL as a long noncoding RNA related to the AS process of HCC. Here, we investigated the exact effect and the mechanism of ANRIL on HCC progress. The ANRIL expression profile was validated using the real-time quantitative polymerase chain reaction assay. The western blot analysis and IHC assay were conducted on candidate targets, including SRSF1 and Anillin. The clinicopathological features of 97 patients were collected and analyzed. Loss-of and gain-of-function experiments were conducted. The dual-luciferase reporter assay was applied to verify the interaction between ANRIL, miR-199a-5p, and SRSF1. Anomalous upregulation of ANRIL in HCC was observed, correlating with worse clinicopathological features of HCC. HCC cell proliferation, mobility, tumorigenesis, and metastasis were impaired by depleting ANRIL. We found that ANRIL acts as a sponger of miRNA-199a-5p, resulting in an elevated level of its target protein SRSF1. The phenotypes induced by ANRIL/miR-199a-5p/SRSF1 alteration are associated with Anillin, a validated HCC promoter. ANRIL is an AS-related lncRNA promoting HCC progress by modulating the miR-199a-5p/SRSF1 axis. The downstream effector of this axis in the development of HCC is Anillin.

Circulating miR-199a and long noncoding-RNA ANRIL as Promising Diagnostic Biomarkers for Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD), involving both Crohn's disease (CD) and ulcerative colitis (UC), represents a chronic, immune-mediated inflammatory disease due to an uncontrolled, ongoing inflammatory response to intestinal bacteria in those with genetic susceptibility. MicroRNA (miRNA) extrusion from relevant remote organs or tissues is reflected in the expression of miRNAs in serum and plasma. Both UC and CD patients had higher blood levels of expressed miR-199a. Long noncoding RNA (lncRNA) ANRIL is a proinflammatory gene that mediates nuclear factor κB to play a role in inflammatory diseases, such as IBD. The aim of the current study is to investigate the potential role of both miR-199a and ANRIL in diagnosing IBD in adult patients. METHODS: Sixty-seven IBD patients diagnosed clinically, radiologically, endoscopically, and histologically were included in this prospective cohort study. Participants were classified into 3 groups: the UC group (n = 35), the CD group (n = 32), and the control group (n = 30). Demographics, history taking, laboratory characteristics, and treatments were recorded. Tumor necrosis factor α, miR-199a, and ANRIL were measured. RESULTS: The findings suggested that miR-199a and ANRIL might be associated with the occurrence or progression of IBD because both genes were substantially expressed in the peripheral blood of patients with this condition. Receiver-operating characteristic curve analysis indicated that the detection of miR-199a and ANRIL had a predictive sensitivity of 62.9% and 88.6% and a specificity of 70.7% and 96.7% for the occurrence of UC cases, respectively, and a predictive sensitivity of 72.4% and 46.9% and a specificity of 96.7% and 34.7% for the occurrence of CD cases, respectively. CONCLUSIONS: Both miR-199a and ANRIL are abundant in the sera of IBD adult Egyptian patients (UC and CD). Both can represent a noninvasive marker for early disease diagnosis.

This study investigated the relation between tumor necrosis factor α, ANRIL, and miR-199a in inflammatory bowel disease patients to determine the probability of using them as prognostic and diagnostic biomarkers, as well as distinguishing between Crohn's disease and ulcerative colitis patients. Our findings showed that ANRIL and miR-199a can represent noninvasive biomarkers for early disease diagnosis.

Severity of coronary artery disease is associated with diminished circANRIL expression: A possible blood based transcriptional biomarker in East Africa.

Antisense Noncoding RNA in the INK4 Locus (ANRIL) is the prime candidate gene at Chr9p21, the well-defined genetic risk locus associated with coronary artery disease (CAD). ANRIL and its transcript variants were investigated for the susceptibility to CAD in adipose tissues (AT) and peripheral blood mononuclear cells (PBMCs) of the study group and the impact of 9p21.3 locus mutations was further analysed. Expressions of ANRIL, circANRIL (hsa_circ_0008574), NR003529, EU741058 and DQ485454 were detected in epicardial AT (EAT) mediastinal AT (MAT), subcutaneous AT (SAT) and PBMCs of CAD patients undergoing coronary artery bypass grafting and non-CAD patients undergoing heart valve surgery. ANRIL expression was significantly upregulated, while the expression of circANRIL was significantly downregulated in CAD patients. Decreased circANRIL levels were significantly associated with the severity of CAD and correlated with aggressive clinical characteristics. rs10757278 and rs10811656 were significantly associated with ANRIL and circANRIL expressions in AT and PBMCs. The ROC-curve analysis suggested that circANRIL has high diagnostic accuracy (AUC: 0.9808, cut-off: 0.33, sensitivity: 1.0, specificity: 0.88). circANRIL has high diagnostic accuracy (AUC: 0.9808, cut-off: 0.33, sensitivity: 1.0, specificity: 0.88). We report the first data demonstrating the presence of ANRIL and its transcript variants expressions in the AT and PBMCs of CAD patients. circANRIL having a synergetic effect with ANRIL plays a protective role in CAD pathogenesis. Therefore, altered circANRIL expression may become a potential diagnostic transcriptional biomarker for early CAD diagnosis.

ANRIL, H19 and TUG1: a review about critical long non-coding RNAs in cardiovascular diseases

Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established.

The linear ANRIL transcript P14AS regulates the NF-κB signaling to promote colon cancer progression.

BACKGROUND: The linear long non-coding RNA P14AS has previously been reported to be dysregulated in colon cancer, but the mechanistic role that P14AS plays in colon cancer progression has yet to be clarified. Accordingly, this study was developed to explore the regulatory functions of ANRIL linear transcript-P14AS in cancer. METHODS: The expression of P14AS, ANRIL, miR-23a-5p and their target genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell supernatants of IL6 and IL8 were measured by Enzyme linked immunosorbent (ELISA) assay. Dual-luciferase reporter assays, RNA immunoprecipitation, or pull-down assays were used to confirm the target association between miR-23a-5p and P14AS or UBE2D3. Cell proliferation and chemosensitivity of NF-κB inhibitor BAY 11-7085 were evaluated by cell counting kit 8 (CCK8). RESULTS: When P14AS was overexpressed in colon cancer cell lines, enhanced TNF-NF-κB signaling pathway activity was observed together with increases in IL6 and IL8 expression. The Pita, miRanda, and RNA hybrid databases revealed the ability of miR-23a-5p to interact with P14AS, while UBE2D3 was further identified as a miR-23a-5p target gene. The results of dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation experiments confirmed these direct interactions among P14AS/miR-23a-5p/UBE2D3. The degradation of IκBa mediated by UBE2D3 may contribute to enhanced NF-κB signaling in these cells. Moreover, the beneficial impact of P14AS on colon cancer cell growth was eliminated when cells were treated with miR-23a-5p inhibitors or UBE2D3 was silenced. As such, these findings strongly supported a role for the UBE2D3/IκBa/NF-κB signaling axis as a mediator of the ability of P14AS to promote colon cancer progression. CONCLUSIONS: These data suggested a mechanism through which the linear ANRIL transcript P14AS can promote inflammation and colon cancer progression through the sequestration of miR-23a-5p and the modulation of NF-κB signaling activity, thus highlighting P14AS as a promising target for therapeutic intervention efforts.

Lnc-ANRIL modulates the immune response associated with NF-κB pathway in LPS-stimulated bovine mammary epithelial cells.

BACKGROUND: The antisense noncoding RNA in the INK4 locus (ANRIL) has been confirmed related to multiple disease progression, but the role and exact mechanisms of lnc-ANRIL in lipopolysaccharide (LPS)-induced inflammation of bovine mammary epithelial cells (MAC-T) remain unclear. AIMS: This manuscript focused on expounding the functional role of lnc-ANRIL through experiments performed in MAC-T. METHODS: At the in vitro level, we established a Bovine mammary epithelial cell (BMEC) cell model of mastitis by LPS treatment. Transfection of siRNA was examined by immunofluorescence localization and RT-qPCR. CCK8, clonogenic assay and EdU were used to detect the proliferation ability of the cells. Cell cycle and apoptosis were detected by flow cytometry and Western blot. The levels of inflammatory factors and oxidative stress markers were detected by ELISA kits. RESULTS: Cell Counting Kit-8, colony formation, and 5-ethynyl-20-deoxyuridine were adopted and the data illustrated that LPS could significantly suppress the cell proliferation, while knockdown of lnc-ANRIL expression obviously promoted MAC-T cell proliferation compared with LPS or LPS + si-NC group. Flow cytometry analysis demonstrated that lnc-ANRIL could induce MAC-T cell apoptosis. In addition, downregulation of lnc-ANRIL affected LPS-induced immune response by regulating inflammatory factor expressions and modulating the nuclear factor kappa B (NF-κB) axis in MAC-T cells. CONCLUSION: Our results suggest that lnc-ANRIL is involved in the regulation of cell proliferation, cell cycle, and cell apoptosis of MAC-T cells, and plays an important role in the inflammatory and immune response of MAC-T cells through the regulation of the NF-κB pathway, proposing new therapeutic strategies for the treatment of innate immune response-related disease such as bovine mastitis.

ANRIL, H19 and TUG1: a review about critical long non-coding RNAs in cardiovascular diseases.

Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established.