Research progress of microRNA in spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.

CYTOR-NFAT1 feedback loop regulates epithelial-mesenchymal transition of retinal pigment epithelial cells.

Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading to permanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-ß1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1's direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD.

The role of long non-coding RNAs in the development of diabetic kidney disease and the involved clinical application.

Diabetic kidney disease (DKD), one of the common microvascular complications of diabetes, is increasing in prevalence worldwide and can lead to End-stage renal disease. However, there are still gaps in our understanding of the pathophysiology of DKD, and both current clinical diagnostic methods and treatment strategies have drawbacks. According to recent research, long non-coding RNAs (lncRNAs) are intimately linked to the developmental process of DKD and could be viable targets for clinical diagnostic decisions and therapeutic interventions. Here, we review recent insights gained into lncRNAs in pathological changes of DKD such as mesangial expansion, podocyte injury, renal tubular injury, and interstitial fibrosis. We also discuss the clinical applications of DKD-associated lncRNAs as diagnostic biomarkers and therapeutic targets, as well as their limitations and challenges, to provide new methods for the prevention, diagnosis, and treatment of DKD.

Exosomal MALAT1 from macrophages treated with high levels of glucose upregulates LC3B expression via miR-204-5p downregulation.

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) plays a critical role in the pathophysiology of diabetes-related complications. However, whether macrophage-derived MALAT1 affects autophagic activity under hyperglycemic conditions is unclear. Therefore, we investigated the molecular regulatory mechanisms of macrophage-derived MALAT1 and autophagy under hyperglycemic conditions. METHODS: Hyperglycemia was induced by culturing macrophages in 25 mM glucose for 1 hour. Exosomes were extracted from the culture media. A rat model of carotid artery balloon injury was established to assess the effect of MALAT1 on vascular injury. Reverse transcription, real-time quantitative polymerase chain reaction, western blotting, immunohistochemical staining, and luciferase activity assays were performed. RESULTS: Stimulation with high levels of glucose significantly enhanced MALAT1 expression in macrophage-derived exosomes. MALAT1 inhibited miR-204-5p expression in macrophage-derived exosomes under hyperglycemic conditions. siRNA-induced silencing of MALAT1 significantly reversed macrophage-derived exosome-induced miR-204-5p expression. Hyperglycemic treatment caused a significant, exosome-induced increase in the expression of the autophagy marker LC3B in macrophages. Silencing MALAT1 and overexpression of miR-204-5p significantly decreased LC3B expression induced by macrophage-derived exosomes. Overexpression of miR-204-5p significantly reduced LC3B luciferase activity induced by macrophage-derived exosomes. Balloon injury to the carotid artery in rats significantly enhanced MALAT1 and LC3B expression, and significantly reduced miR-204-5p expression in carotid artery tissue. Silencing MALAT1 significantly reversed miR-204-5p expression in carotid artery tissue after balloon injury. MALAT1 silencing or miR-204-5p overexpression significantly reduced LC3B expression after balloon injury. CONCLUSION: This study demonstrated that hyperglycemia upregulates MALAT1 . MALAT1 suppresses miR-204-5p expression and counteracts the inhibitory effect of miR-204-5p on LC3B expression in macrophages to promote vascular disease.

Adipose exosomal noncoding RNAs: Roles and mechanisms in metabolic diseases.

Exosomes are extracellular vesicles, measuring 40-160 nm in diameter, that are released by many cell types and tissues, including adipose tissue. Exosomes are critical mediators of intercellular communication and their contents are complex and diverse. In recent years, accumulating evidence has proved that multiple adipose tissue-derived exosomal noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in the pathogenesis of diverse metabolic diseases, such as obesity. In this narrative review, we focus on the adipose tissue-derived exosomal ncRNAs, especially exosomal miRNAs, and their dysregulation in multiple types of metabolic diseases. A deeper understanding of the role of adipose tissue-derived exosomal ncRNAs may help provide new diagnostic and treatment methods for metabolic diseases.

Pathological role of LncRNAs in immune-related disease via regulation of T regulatory cells.

Human regulatory T cells (Tregs) are essential in pathogenesis of several diseases such as autoimmune diseases and cancers, and their imbalances may be promoting factor in these disorders. The development of the proinflammatory T cell subset TH17 and its balance with the generation of regulatory T cells (Treg) is linked to autoimmune disease and cancers. Long non-coding RNAs (lncRNAs) have recently emerged as powerful regulatory molecules in a variety of diseases and can regulate the expression of significant genes at multiple levels through epigenetic regulation and by modulating transcription, post-transcriptional processes, translation, and protein modification. They may interact with a wide range of molecules, including DNA, RNA, and proteins, and have a complex structural makeup. LncRNAs are implicated in a range of illnesses due to their regulatory impact on a variety of biological processes such as cell proliferation, apoptosis, and differentiation. In this regard, a prominent example is lncRNA NEAT1 which several studies have performed to determine its role in the differentiation of immune cells. Many other lncRNAs have been linked to Treg cell differentiation in the context of immune cell differentiation. In this study, we review recent research on the various roles of lncRNAs in differentiation of Treg cell and regulation of the Th17/Treg balance in autoimmune diseases and tumors in which T regs play an important role.

Long Non-Coding RNA LPP-AS2 Plays an Anti-Tumor Role in Thyroid Carcinoma by Regulating the miR-132-3p/OLFM1 Axis.

The cancer-promoting function of the long non-coding RNA (lncRNA) LPP-AS2 has been documented in different cancers. Nonetheless, its role in thyroid carcinoma (THCA) remains unestablished. Reverse transcription quantitative polymerase chain reaction and Western blotting were conducted to estimate the expressions of lncRNA LPP-AS2, miR-132-3p, and OLFM1. The THCA cells' functions were assessed through CCK8 assays, Transwell invasion assays, scratch wound-healing migration assays, and quantification of caspase-3 activity. The in vivo assays were also implemented to assess tumor growth. Luciferase reporter and RNA immuno-precipitation assay (RIPA) experiments were executed to elucidate the interactions of miR-132-3p with lncRNA LPP-AS2 and OLFM1. THCA tissues and cells exhibited poor lncRNA LPP-AS2 and OLFM1 expressions and a robust expression of miR-132-3p. Overexpressing lncRNA LPP-AS2 constrained THCA cell proliferation, migration, and invasion and improved caspase-3 activity. The anti-tumor function of lncRNA LPP-AS2 was also validated in vivo. miR-132-3p had an interplay with lncRNA LPP-AS2 and OLFM1. Functionally, overexpressing miR-132-3p promoted the malignant THCA cell phenotypes. However, that tumor promotion was abolished by the additional overexpression of lncRNA LPP-AS2. The in vitro experiments also demonstrated that the repressive effect of OLFM1 overexpression on THCA cell malignant action could be offset by the miR-132-3p mimic. lncRNA LPP-AS2 impedes THCA progression via the miR-132-3p/OLFM1 axis. Our findings contribute a potential strategy in interfering with THCA progression.

lncRNA NEAT1 mediates LPS-induced pyroptosis of BEAS-2B cells via targeting miR-26a-5p/ROCK1 axis.

Acute lung injury (ALI) is an adverse disease of the respiratory system, and one of its prevalent causes is sepsis induction. Cell pyroptosis facilitates the progression of ALI and lncRNAs play critical roles in ALI. Thus, this research seeks to investigate the specific mechanism of NEAT1 in sepsis-ALI.BEAS-2B cells were exposed to lipopolysaccharide (LPS) to construct a cell model of sepsis-induced ALI. The gene and protein expression were assessed using qRT-PCR and western blot. Cell viability was identified by CCK-8. Cell death was discovered using PI staining. The secretion of IL-1ß and IL-18 was examined using ELISA. The interconnections among NEAT1, miR-26a-5p, and ROCK1 were confirmed using starbase, luciferase assay, and RIP.LPS treatment augmented NEAT1 and ROCK1 levels while mitigating miR-26a-5p level in BEAS-2B cells. Additionally, LPS treatment facilitated cell death and cell pyroptosis, whereas NEAT1 silencing could reverse these effects in BEAS-2B cells. Mechanistically, NEAT1 positively mediated ROCK1 expression by targeting miR-26a-5p. Furthermore, miR-26a-5p inhibitor offset NEAT1 depletion-mediated suppressive effects on cell death and cell pyroptosis. ROCK1 upregulation decreased the inhibitory impacts produced by miR-26a-5p overexpression on cell death and cell pyroptosis. Our outcomes demonstrated NEAT1 could reinforce LPS-induced cell death and cell pyroptosis by repressing the miR-26a-5p/ROCK1 axis, thereby worsening ALI caused by sepsis. Our data indicated NEAT1, miR-26a-5p, and ROCK1 might be biomarkers and target genes for relieving sepsis-induced ALI.

LncRNA TCONS_00323213 Promotes Myogenic Differentiation by Interacting with PKNOX2 to Upregulate MyoG in Porcine Satellite Cells.

Myogenic differentiation is a complex biological process that is regulated by multiple factors, among which long noncoding RNAs (lncRNAs) play an essential role. However, in-depth studies on the regulatory mechanisms of long noncoding RNAs (lncRNAs) in myogenic differentiation are limited. In this study, we characterized the role of the novel lncRNA TCONS_00323213, which is upregulated during porcine skeletal muscle satellite cell (PSC) differentiation in myogenesis. We found that TCONS_00323213 affected the proliferation and differentiation of PSC in vitro. We performed quantitative polymerase chain reaction (qPCR), 5-ethynyl-20-deoxyuridine (EdU), western blotting, immunofluorescence staining, pull-down assays, and cleavage under targets and tagmentation (CUT and Tag) assays to clarify the effects and action mechanisms of TCONS_00323213. LncRNA TCONS_00323213 inhibited myoblast proliferation based on analyses of cell survival rates during PSC proliferation. Functional analyses revealed that TCONS_00323213 promotes cell differentiation and enhances myogenin (MyoG), myosin heavy chain (MyHC), and myocyte enhancer factor 2 (MEF2C) during myoblast differentiation. As determined by pull-down and RNA immunoprecipitation (RIP) assays, the lncRNA TCONS_00323213 interacted with PBX/Knotted Homeobox 2 (PKNOX2). CUT and Tag assays showed that PKNOX2 was significantly enriched on the MyoG promoter after lncRNA TCONS_00323213 knockdown. Our findings demonstrate that the interaction between lncRNA TCONS_00323213 and PKNOX2 relieves the inhibitory effect of PKNOX2 on the MyoG promoter, increases its expression, and promotes PSC differentiation. This novel role of lncRNA TCONS_00323213 sheds light on the molecular mechanisms by which lncRNAs regulate porcine myogenesis.

MiR-326 regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis.

The dysregulation of microRNAs plays a critical role in the development of rheumatoid arthritis (RA). This study aims to explore the functional significance of miR-326 in RA. The RT-qPCR results showed that miR-326 was downregulated in synovial tissues of RA patients and RA fibroblast-like synoviocytes (RA-FLS). We found that miR-326 could target and reduce the expression of inhibitor of DNA binding 1 (Id1). MTT assay and flow cytometry were conducted to explore the biological function of miR-326. Our data revealed that the upregulation of miR-326 suppressed cell proliferation and induced apoptosis in RA-FLS. In collagen-induced arthritis mice, intraarticular injection of lentivirus carrying miR-326 overexpression vectors could reduce the arthritis score and attenuate synovial inflammation and cartilage destruction. We also found that long non-coding RNA-Ewing sarcoma-associated transcript 1 (lncRNA-EWSAT1) was significantly increased in RA synovial tissues and RA-FLS. The RNA immunoprecipitation and RNA pull-down assay indicated that lncRNA-EWSAT1 directly bound and negatively regulated the expression of miR-326. Knockdown of lncRNA-EWSAT1 could upregulate miR-326 expression and attenuate its proliferation inhibition and apoptosis induction effect in RA-FLS.  In conclusion, the lncRNA-EWSAT1/miR-326 axis might provide a novel therapeutic target in the treatment of RA.

LncSNHG14 promotes nutlin3a resistance by inhibiting ferroptosis via the miR-206 /SLC7A11 axis in osteosarcoma cells.

The most prevalent form of primary osseous malignant tumor in adolescents and children is osteosarcoma (OS). A combination of surgery and neoadjuvant/post-surgery chemotherapy is currently the standard therapy. While the chemoresistance associated with OS generally leads to poor efficacy of therapeutic agents, the relevant molecular interaction is still elusive. Here, the lncRNA (long non-coding RNA) SNHG14 was found to be significantly upregulated in the nutlin3a-resistant OS cell line NR-SJSA1 and contributes to treatment resistance by suppressing ferroptosis. In NR-SJSA1 cells, knockdown of LncRNA SNHG14 resulted in a reversal of drug resistance and activation of ferroptosis, which disappeared when ferrostatin-1, a ferroptosis inhibitor, was added. Mechanistically, lncRNA SNHG14 targeted and down-regulated the expression of miR-206, further affecting the common ferroptosis inhibitor SLC7A11, and preventing NR-SJSA1 cells from undergoing ferroptosis. In conclusion, our findings highlight the involvement of lncRNA SNHG14 in ferroptosis and chemotherapy resistance of nutlin3a-resistant NR-SJSA1 cells, thus shedding new insight on how to overcome drug resistance in osteosarcoma cells and improve treatment efficacy.

Long noncoding RNA CHROMR regulates antiviral immunity in humans.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their contribution to immune regulation in humans remains poorly understood. Here, we report that the primate-specific lncRNA CHROMR is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. CHROMR depletion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli. Mechanistically, we show that CHROMR sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, CHROMR expression is essential to restrict viral infection of macrophages. Our findings identify CHROMR as a key arbitrator of antiviral innate immune signaling in humans.

Long non­coding RNA PART1: dual role in cancer.

Increasing evidence has shown that long non-coding RNAs (lncRNAs), which are non-coding endogenous single-stranded RNAs, play an essential role in various physiological and pathological processes through transcriptional interference, post-transcriptional regulation, and epigenetic modification. Moreover, lncRNAs, as oncogenes or tumor suppressor genes, play an important role in the occurrence and development of human cancers. Prostate androgen-regulated transcript 1 (PART1) was initially identified as a carcinogenic lncRNA in prostate adenomas. The upregulated expression of PART1 plays a tumor-promoting role in liver, prostate, lung cancers, and other tumors. In contrast, the expression of PART1 is downregulated in esophageal squamous cell carcinoma, glioma, and other tumors, which may inhibit the tumor. PART1 plays a dual role in cancer and regulates cell proliferation, apoptosis, invasion, and metastasis through a variety of potential mechanisms. These findings suggest that PART1 is a promising tumor biomarker and therapeutic target. This article reviews the biological functions, related mechanisms, and potential clinical significance of PART1 in a variety of human cancers.

Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF.

Enhancer RNAs (eRNAs) are long non-coding RNAs that originate from enhancers. Although eRNA transcription is a canonical feature of activated enhancers, the molecular features required for eRNA function and the mechanism of how eRNAs impinge on target gene transcription have not been established. Thus, using eRNA-dependent RNA polymerase II (Pol II) pause release as a model, we here investigate the requirement of sequence, structure and length of eRNAs for their ability to stimulate Pol II pause release by detaching NELF from paused Pol II. We find eRNAs not to exert their function through common structural or sequence motifs. Instead, eRNAs that exhibit a length >200 nucleotides and that contain unpaired guanosines make multiple, allosteric contacts with NELF subunits -A and -E to trigger efficient NELF release. By revealing the molecular determinants of eRNA function, our study establishes eRNAs as an important player in Pol II pause release, and it provides new insight into the regulation of metazoan transcription.

LncRNA PVT1 is increased in renal cell carcinoma and affects viability and migration in vitro.

BACKGROUND: Renal cell carcinoma is difficult to diagnose and unpredictable in disease course and severity. There are no specific biomarkers for diagnosis and prognosis estimation feasible in clinical practice. Long non-coding RNAs (lncRNAs) have emerged as potent regulators of gene expression in recent years. Aside from their cellular role, their expression patterns could be used as a biomarker of ongoing pathology. METHODS: In this work, we used next-generation sequencing for global lncRNA expression profiling in tumor and non-tumor tissue of RCC patients. The four candidate lncRNAs have been further validated on an independent cohort. PVT1, as the most promising lncRNA, has also been studied using functional in vitro tests. RESULTS: Next-generation sequencing showed significant dysregulation of 1163 lncRNAs; among them top 20 dysregulated lncRNAs were AC061975.7, AC124017.1, AP000696.1, AC148477.4, LINC02437, GATA3-AS, LINC01762, LINC01230, LINC01271, LINC01187, LINC00472, AC007849.1, LINC00982, LINC01543, AL031710.1, and AC019197.1 as down-regulated lncRNAs; and SLC16A1-AS1, PVT1, LINC0887, and LUCAT1 as up-regulated lncRNAs. We observed statistically significant dysregulation of PVT1, LUCAT1, and LINC00982. Moreover, we studied the effect of artificial PVT1 decrease in renal cell line 786-0 and observed an effect on cell viability and migration. CONCLUSION: Our results show not only the diagnostic but also the therapeutic potential of PVT1 in renal cell carcinoma.

Expression of LINC00847 in Peripheral Blood Mononuclear Cells of Children with Asthma and Its Prediction between Asthma Exacerbation and Remission.

Objective: Asthma is defined as a heterogeneous disease that is usually characterized by chronic airway inflammation. Long noncoding RNAs play important roles in various biological processes including inflammation. To know more about the relationships between lncRNAs and asthma, we sought to the role of LINC00847 in peripheral blood mononuclear cells (PBMCs) of children with asthma exacerbation or asthma remission. Methods: Microarray analysis was performed on GSE143192 and GSE165934 datasets to screen differentially expressed lncRNAs (DElncRNAs) in human PBMCs between asthma patients and normal controls. LINC00847 was selected from DElncRNAs in human PBMCs between asthma patients and normal controls for further investigation. The expression levels of LINC00847 were quantified in PBMCs collected from 54 children with asthma exacerbation, 54 children with asthma remission, and 54 healthy children by real-time qPCR. The forced expiratory volume in the first second in percent predicted values (FEV1%), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), and peak expiratory flow rate (PEF%) were tested for evaluation of lung function. The concentration of immunoglobulin E (IgE) and eosinophil count was examined. The serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17A were determined by the ELISA method. Results: The expression level of LINC00847 in PBMCs of asthma exacerbation children was remarkably higher than that in PBMCs of asthma remission children and healthy children (p < 0.001); the expression level of LINC00847 in PBMCs of asthma remission children was notably higher than that in PBMCs of healthy children (p < 0.001). Pearson correlation analysis revealed that the expression levels of LINC00847 in PBMCs of asthma children were negatively correlated with FEV1% (r = -0.489), FEV1/FVC (r = -0.436), PEF% (r = -0.626), and IFN-γ level (r = -0.614) of asthma children, but positively correlated with IgE concentration (r = 0.680), eosinophil count (r = 0.780), IL-4 (r = 0.524), and IL-17A (r = 0.622) levels. When LINC00847 expression was used to distinguish asthma exacerbation from asthma remission, a 0.871 AUC (95% CI: 0.805-0.936) was yielded with sensitivity of 79.63% and specificity of 77.78%. Conclusion: The study demonstrates that increased LINC00847 expression may be associated with the development and progression of asthma, possibly serving as a novel biomarker for predicting asthma exacerbation from asthma remission.

Long noncoding RNA Kcnq1ot1 prompts lipopolysaccharide-induced acute lung injury by microRNA-7a-5p/Rtn3 axis.

BACKGROUND: Long noncoding RNA (lncRNA)-regulated mechanism in acute lung injury (ALI) has attracted special interests in study researches. We planned to disclose whether KCNQ1 overlapping transcript 1 (Kcnq1ot1) is involved in ALI and its mechanism. METHODS: The lipopolysaccharide (LPS)-induced ALI model was established in mice. Kcnq1ot1, microRNA (miR)-7a-5p and Reticulon 3 (Rtn3) levels were measured in lung tissues of mice. The vector that changed Kcnq1ot1, miR-7a-5p and Rtn3 expression was injected into LPS-treated mice, and pathological damage, fibrosis, apoptosis and inflammatory response were subsequently examined in lung tissues. The relation between Kcnq1ot1 and miR-7a-5p, and that between miR-7a-5p and Rtn3 were identified. RESULTS: Kcnq1ot1 and Rtn3 expression increased while miR-7a-5p expression decreased in LPS-treated mice. Reduced Kcnq1ot1 or elevated miR-7a-5p alleviated pathological damage, fibrosis, apoptosis and inflammatory response in ALI mice, while overexpressed Rtn3 worsened ALI in mice. Downregulation of Rtn3 reversed the exacerbation of miR-7a-5p downregulation in ALI mice. Kcnq1ot1 competitively bound to miR-7a-5p and miR-7a-5p negatively mediated Rtn3 expression. CONCLUSION: Our experiments evidence that silencing Kcnq1ot1 upregulates miR-7a-5p to suppress Rtn3 expression, thereby diminishing LPS-induced ALI.

The Role of ANRIL in Atherosclerosis.

There is a huge number of noncoding RNA (ncRNA) transcripts in the cell with important roles in modulation of different mechanisms. ANRIL is a long ncRNA with 3.8 kb length that is transcribed in the opposite direction of the INK4/ARF locus in chromosome 9p21. It was shown that polymorphisms within this locus are associated with vascular disorders, notably coronary artery disease (CAD), which is considered as a risk factor for life-threatening events like myocardial infarction and stroke. ANRIL is subjected to a variety of splicing patterns producing multiple isoforms. Linear isoforms could be further transformed into circular ones by back-splicing. ANRIL regulates genes in atherogenic network in a positive or negative manner. This regulation is implemented both locally and remotely. While CAD is known as a proliferative disorder and cell proliferation plays a crucial role in the progression of atherosclerosis, the functions of ANRIL and CAD development are intertwined remarkably. This makes ANRIL a suitable target for diagnostic, prognostic, and even therapeutic aims. In this review, we tried to present a comprehensive appraisal on different aspects of ANRIL including its location, structure, isoforms, expression, and functions. In each step, the contribution of ANRIL to atherosclerosis is discussed.

LncRNA FIRRE functions as a tumor promoter by interaction with PTBP1 to stabilize BECN1 mRNA and facilitate autophagy.

Long non-coding RNAs (lncRNAs) play critical functions in various cancers. Firre intergenic repeating RNA element (FIRRE), a lncRNA located in the nucleus, was overexpressed in colorectal cancer (CRC). However, the detailed mechanism of FIRRE in CRC remains elusive. Results of RNA sequence and qPCR illustrated overexpression of FIRRE in CRC cell lines and tissues. The aberrant expression of FIRRE was correlated with the migration, invasion, and proliferation in cell lines. In accordance, it was also associated with lymphatic metastasis and distant metastasis in patients with CRC. FIRRE was identified to physically interact with Polypyrimidine tract-binding protein (PTBP1) by RNA pull-down and RNA immunoprecipitation (RIP). Overexpression of FIRRE induced the translocation of PTBP1 from nucleus to cytoplasm, which was displayed by immunofluorescence and western blot. In turn, delocalization of FIRRE from nucleus to cytoplasm is observed after the loss of PTBP1. The RNA-protein complex in the cytoplasm directly bound to BECN1 mRNA, and the binding site was at the 3' end of the mRNA. Cells with FIRRE and PTBP1 depletion alone or in combination were treated by Actinomycin D (ACD). Results of qPCR showed FIRRE stabilized BECN1 mRNA in a PTBP1-medieated manner. In addition, FIRRE contributed to autophagy activity. These findings indicate FIRRE acts as an oncogenic factor in CRC, which induces tumor development through stabilizing BECN1 mRNA and facilitating autophagy in a PTBP1-mediated manner.

Long non-coding RNA PAARH promotes hepatocellular carcinoma progression and angiogenesis via upregulating HOTTIP and activating HIF-1α/VEGF signaling.

Hepatocellular carcinoma (HCC) is one of the leading lethal malignancies and a hypervascular tumor. Although some long non-coding RNAs (lncRNAs) have been revealed to be involved in HCC. The contributions of lncRNAs to HCC progression and angiogenesis are still largely unknown. In this study, we identified a HCC-related lncRNA, CMB9-22P13.1, which was highly expressed and correlated with advanced stage, vascular invasion, and poor survival in HCC. We named this lncRNA Progression and Angiogenesis Associated RNA in HCC (PAARH). Gain- and loss-of function assays revealed that PAARH facilitated HCC cellular growth, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumor growth and angiogenesis in vivo. PAARH functioned as a competing endogenous RNA to upregulate HOTTIP via sponging miR-6760-5p, miR-6512-3p, miR-1298-5p, miR-6720-5p, miR-4516, and miR-6782-5p. The expression of PAARH was significantly positively associated with HOTTIP in HCC tissues. Functional rescue assays verified that HOTTIP was a critical mediator of the roles of PAARH in modulating HCC cellular growth, apoptosis, migration, and invasion. Furthermore, PAARH was found to physically bind hypoxia inducible factor-1 subunit alpha (HIF-1α), facilitate the recruitment of HIF-1α to VEGF promoter, and activate VEGF expression under hypoxia, which was responsible for the roles of PAARH in promoting angiogenesis. The expression of PAARH was positively associated with VEGF expression and microvessel density in HCC tissues. In conclusion, these findings demonstrated that PAARH promoted HCC progression and angiogenesis via upregulating HOTTIP and activating HIF-1α/VEGF signaling. PAARH represents a potential prognostic biomarker and therapeutic target for HCC.