Expression Of MIAT Research Articles

LncRNA CDKN2B-AS1 is downregulated in patients with ventricular fibrillation in acute myocardial infarction.

Ventricular fibrillation (VF) in acute myocardial infarction (AMI) is the main cause of deaths occurring in the acute phase of an ischemic event. Although it is known that genetics may play an important role in this pathology, the possible role of long non-coding RNAs (lncRNA) has never been studied. Therefore, the aim of this work is to study the expression of 10 lncRNAs in patients with and without VF in AMI. For this purpose, the expression of CDKN2B-AS1, KCNQ1OT1, LIPCAR, MALAT1, MIAT, NEAT1, SLC16A1-AS1, lnc-TK2-4:2, TNFRSF14-AS1, and UCA1 were analyzed. After the analysis and Bonferroni correction, the lncRNA CDKN2B-AS showed a statistical significance lower expression (P values of 2.514 x 10-5). In silico analysis revealed that six proteins could be related to the possible effect of lncRNA CDKN2B-AS1: AGO3, PLD4, POU4F1, ZNF26, ZNF326 and ZNF431. These in silico proteins predicted to have a low cardiac expression, although there is no literature indicating a potential relationship with VF in AMI. Thus, the lncRNA CDKN2B-AS1 shows a significant lower expression in patients with VF in AMI vs patients without VF in AMI. Literature data suggest that the role of CDKN2B1-AS is related to the miR-181a/SIRT1 pathway.

Зміни експресії довгих некодуючих РНК H19, TUG1, GAS5, MIAT при ішемії-реперфузії міокарда

Long non-coding RNAs (lncRNAs) are the most numerous group of transcripts performing various functions, including the development of cardiovascular pathologies. We investigated the changes in expression of four long non-coding RNAs (H19, TUG1, GAS5, MIAT) under conditions of anoxia-reoxygenation in neonatal rat cardiomyocyte culture and ischemia-reperfusion in adult Wistar rats. A significant decrease in the expression of all four long non-coding RNAs in cell culture under experimental conditions was established. The regime of prolonged anoxia-reoxygenation led to a sharp increase in the expression level of long non-coding RNA MIAT by twice, but compared to normoxia, these changes were not significant. After ischemia-reperfusion in rat myocardium, the content of long non-coding RNA TUG1 increased by 22 times, while the expression of H19 decreased by 3.79 times, and in rat plasma, the expression of long non-coding RNA MIAT increased by 3.79 times. The obtained results allow considering long non-coding RNAs H19 and TUG1 as potential targets in ischemic myocardial injury, and MIAT as a biomarker of cardiovascular pathologies.

Downregulating lncRNA MIAT attenuates apoptosis of podocytes exposed to high glucose.

Diabetic nephropathy (DN), a destructive complication of diabetes mellitus (DM), is one of the leading causes of end-stage renal disease (ESRD). This study aimed to investigate the role of long non-coding RNA (lncRNA) MIAT in high-glucose (HG)-induced podocyte injury associated with DN. Three human kidney podocyte (HKP) cultures were treated with HG to mimic DN. Expression of lncRNA MIAT, podocyte-specific and injury-related proteins, and apoptosis were assessed before and after MIAT knockdown using MIAT shRNAs. MIAT expression was upregulated in HKPs in response to glucose stress. HG treatment resulted in a significant increase in the apoptotic rate, Bax level, and levels of injury-related proteins desmin, fibroblast-specific protein 1 (FSP-1), and smooth muscleα-actin (α-SMA), and a significant reduction in Bcl-2 levels and the levels of podocyte-specific proteins synaptopodin and podocin. Transfection of HKPs with shRNAs significantly reduced MIAT levels (p < 0.05) and attenuated apoptosis in HG-medium. Correspondingly, the levels of synaptopodin and podocin were upregulated, and desmin, FSP-1, and α-SMA were reduced (p < 0.05). Western blot analysis also showed that anti-apoptotic active caspase-3 and Bax and proapoptotic Bcl-2 were elevated and decreased, respectively, after MIAT knockdown, suggesting that apoptosis pathways are deactivated after MIAT downregulation. High glucose upregulates MIAT level in HKPs and induces cellular injury. Knockdown of MIAT alleviates the injury likely via deactivating apoptosis pathways.

Potentilla reptans L. preconditioning regulates H19 and MIAT long noncoding RNAs in H9C2 myoblasts Ischemia/Reperfusion model

The present study aimed to evaluate the effect of the ethyl acetate fraction of P. reptans root (PEF) preconditioning on expressions of lncRNAs H19 and MIAT in H9C2 myoblasts I/R injury.H9C2 cells were treated with different concentrations ranging from (10–400 µg/ml) of PEF for 24 h, followed by simulation of I/R condition. For I/R experiments, H9C2 cells were subjected with the oxygen and glucose deprivation for 2 h.H9C2 cell viability was significantly enhanced by PEF preconditioning under I/R condition in a concentration-dependent manner up to 200 µg/ml as a EC50. The PEF significantly diminished the expression of lncRNA MIAT and rate of apoptosis against the I/R group. In addition, PEF pretreated before stimulation I/R condition increased H19 expression compared to the normal PEF group with no statistically significant differences between groups. Hence, the results suggest that PEF can protect cardiomyocytes during hypoxia-induced myocardial cell injury by targeting specific involved genes.

LncRNA Miat knockdown protects against pirarubicin-induced cardiotoxicity by targeting miRNA-129-1-3p.

Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. The aim of this study was to investigate the protective effect and mechanism of knockdown of lncRNA Miat in THP-induced cardiotoxicity. The extent of damage to immortalized cardiomyocytes in mice was assessed by CCK8, TUNEL, ROS, Ca2+ , RT-qPCR, and Western blot. The relative levels of Miat in THP-treated cardiomyocytes (HL-1) were measured. The protective effect of Miat on THP-treated HL-1 was assessed. The binding relationship between lncRNA Miat and mmu-miRNA-129-1-3p was verified by a dual luciferase reporter gene assay. The protective role of Miat/miRNA-129-1-3p in THP-induced HL-1 was explored by performing a rescue assay. THP reduced cell viability, induced apoptosis, triggered oxidative stress and calcium overload. Expression of Miat in HL-1 was significantly elevated after THP treatment. Miat knockdown significantly alleviated the cardiotoxicity of THP. MiR-129-1-3p is a direct target of Miat. Knockdown of miR-129-1-3p reversed the protective effect of Miat knockdown on HL-1. Miat knockdown can alleviate THP-induced cardiomyocyte injury by regulating miR-129-1-3p.

LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition

Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated during liver fibrosis. Silencing MIAT leads to the suppression of hepatic stellate cell (HSC) proliferation and collagen expression. Double immunofluorescence analysis additionally demonstrates that MIAT inhibition leads to the suppression of type I collagen and α-SMA in vitro. In vivo, MIAT knockdown contributes to the inhibition of fibrosis progression and collagen accumulation. MIAT is confirmed as a target of miR-3085-5p, and the co-location of MIAT and miR-3085-5p is found in HSC cytoplasm. Interestingly, there is a negative correlation between MIAT expression and miR-3085-5p level in cirrhotic patients as well as activated HSCs. In addition, the effects of MIAT inhibition on HSC inactivation are blocked down by miR-3085-5p inhibitor. YAP is a target of miR-3085-5p. Reduced YAP caused by loss of MIAT is reversed by miR-3085-5p inhibitor. Notably, YAP knockdown results in the suppression of MIAT-mediated epithelial-to-mesenchymal transition (EMT) process. In conclusion, we demonstrate that MIAT enhances the activation of HSCs, at least in part, via miR-3085-5p/YAP/EMT signaling pathway.

The effect of daidzein on renal injury in ovariectomized rats: interaction of angiotensin receptors and long non-coding RNAs H19, GAS5, MIAT, and Rian.

Renin-angiotensin system (RAS) is prominently associated with renal pathophysiology in postmenopausal women. Long non-coding RNAs (lncRNAs) H19, GAS5, MIAT, and Rian have been linked to the pathogenesis of renal injury. This study aimed to evaluate the beneficial effects of daidzein on unilateral ureteral obstruction (UUO) induced-renal injury in ovariectomized (OVX) rats through interaction with angiotensin AT1, Mas receptors, and lncRNAs. 84 female rats were ovariectomized (OVX) two weeks before performing obstruction of the left kidney ureter (UUO). The animals were then randomly divided into four main groups (n=21): Sham+DMSO, UUO+DMSO, UUO+17β-Estradiol (E2) (positive control), and UUO+daidzein. Each main group comprised three subgroups (n=7) and were treated with saline, A779 (MasR antagonist), or losartan (AT1R antagonist) for 15 days. On day 16, the animals were euthanized, and the left kidneys were harvested for histopathology and lncRNAs expression assays. UUO significantly increased kidney tissue damage score (KTDS) in the UUO rats, increased the expression of H19 and MIAT, and decreased the expression of GAS5 and Rian. Daidzein alone and in co-treatment with losartan or A779 reversed these effects. Daidzein with 1 mg/kg dose was more effective than E2. Daidzein alone and in co-treatment with A779 and losartan improved renal injury in UUO rats and recovered dysregulated expression of UUO-related lncRNAs through modulating MasR and AT1R receptors, associating with modulation of the expression of lncRNAs. Daidzein could be considered a renoprotective phytoestrogen substitute for E2 therapy in postmenopausal women suffering from renal diseases.

LncRNA Miat promotes neuropathic pain through miR-362-3p/BAMBI signaling axis

The treatment of neuropathic pain (NP) has become an important subject to be studied and solved urgently in clinical practice. The role of long noncoding RNAs (lncRNAs) in NP development is becoming clear. Therefore, this study aimed to investigate the role and mechanism of lncRNA Miat in NP. In this study, chronic contractionary injury (CCI) mouse NP model was performed. Firstly, the effects of Miat on pain behavior in mice and the expression levels of pro-inflammatory cytokines and pro-inflammatory proteins in spinal cord tissue were explored by interfering with the expression of Miat. Then, Miat-targeted signaling pathway was predicted by bioinformatics and verified by dual luciferase reporter gene and RNA pull down. Finally, the mechanism of Miat was confirmed by the rescue experiments. Our results demonstrated that Miat knockdown alleviated paw withdrawal threshold, paw withdrawal latency, cold hyperalgesia frequency and neuroinflammation in CCI mice. MiR-362-3p was able to bind to Miat and BAMBI. Overall, Miat upregulated BAMBI by inhibiting miR-362-3p, thereby promoting the occurrence and development of NP. This study analyzed the possibility and effectiveness of targeting Miat for NP clinical treatment, in order to provide new ideas and technical methods for NP gene therapy.

Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis

BackgroundMyocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients’ lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a variety of regulatory functions in myocardial fibrosis, but whether electroacupuncture can inhibit myocardial fibrosis by regulating lncRNA has rarely been reported.MethodsIn this study, we constructed myocardial fibrosis rat models using isoproterenol (ISO) and treated rats with electroacupuncture at PC6 point and non-point as control. Hematoxylin–eosin, Masson and Sirius Red staining were performed to assess the pathological changes and collagen deposition. The expression of fibrosis-related markers in rat myocardial tissue were detected by RT-qPCR and Western blot. Miat, an important long non-coding RNA, was selected to study the regulation of myocardial fibrosis by electroacupuncture at the transcriptional and post-transcriptional levels. In post-transcriptional level, we explored the myocardial fibrosis regulation effect of Miat on the sponge effect of miR-133a-3p. At the transcriptional level, we studied the formation of heterodimer PPARG–RXRA complex and promotion of the TGF-β1 transcription.ResultsMiat was overexpressed by ISO injection in rats. We found that Miat can play a dual regulatory role in myocardial fibrosis. Miat can sponge miR-133a-3p in an Ago2-dependent manner, reduce the binding of miR-133a-3p target to the 3ʹUTR region of CTGF mRNA and improve the protein expression level of CTGF. In addition, it can also directly bind with PPARG protein, inhibit the formation of heterodimer PPARG–RXRA complex and then promote the transcription of TGF-β1. Electroacupuncture at PC6 point, but not at non-points, can reduce the expression of Miat, thus inhibiting the expression of CTGF and TGF-β1 and inhibiting myocardial fibrosis.ConclusionWe revealed that electroacupuncture at PC6 point can inhibit the process of myocardial fibrosis by reducing the expression of lncRNA Miat, which is a potential therapeutic method for myocardial fibrosis.

Novel insights into bicuspid aortic valve (BAV) aortopathy: Long non-coding RNAs TUG1 and MIAT are differentially expressed in BAV ascending aortas

BackgroundWhilst a combination of genetically mediated vulnerability and hemodynamic insult is suspected to contribute to bicuspid aortic valve (BAV) aortopathy, the underlying pathophysiological mechanisms are poorly understood. MethodsUtilizing RT-qPCR, we compared the expression of 28 potentially relevant long non-coding RNA (lncRNA) in aortic tissue from BAV patients undergoing aortic surgery for aortopathy, to healthy controls. Relative lncRNA expression was measured using ΔΔCT, with fold-change calculated as RQ=2−ΔΔCT. ResultsWhen comparing samples from BAV patients (n=29, males n=25; median age 58 years, Q1-Q3 51–65, maximum aortic dimension 50±5 mm) with healthy controls (n=7; males n=4, P=.12; median age 39 years, Q1-Q3 18-47, P=.001), there were two differentially expressed lncRNA: TUG1 expression was significantly lower in BAV aortic tissue (RQ 0.59, 95% CI 0.50–0.69, P=.02), whilst MIAT expression was significantly higher (RQ 2.87, 95% CI 1.96–4.20, P=.01). Sensitivity analysis including only patients with normal BAV function showed similar trends of differential expression of TUG1 (RQ 0.69, 95% CI 0.50-0.90, P=.29) and MIAT (RQ 2.55, 95% CI 1.21-5.36, P=.29) compared to controls. ConclusionsLncRNA TUG1 and MIAT are differentially expressed in BAV aortopathy compared to healthy controls, independent of BAV hemodynamics. Aberrant lncRNA expression may be involved in the pathogenesis of BAV aortopathy

LncRNA MIAT targets miR-411-5p/STAT3/PD-L1 axis mediating hepatocellular carcinoma immune response.

Emerging evidences have shown that long noncoding RNA (lncRNA) plays an important role in the immune escape of cancer cells. Our previous study has demonstrated that lncRNA MIAT is associated with the immune infiltration of hepatocellular carcinoma (HCC). However, the underlying mechanism of MIAT regulating the PD-L1-mediated immune escape of HCC is poorly understood. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of MIAT and PD-L1 mRNA in HCC. The relationship between MIAT, miR-411-5p, STAT3 and PD-L1 was explored by dual-luciferase reporter assay, cytotoxicity assay, Western blot and RNA immunoprecipitation (RIP). In addition, the xenograft model was established to determine the effect of MIAT on PD-L1 expression in vivo. We found that MIAT and PD-L1 were significantly upregulated in HCC tissues and the expression of PD-L1 was regulated by MIAT. The knockdown of MIAT enhanced the cytotoxicity of T cells on HCC cells. MIAT negatively regulated miR-411-5p expression, upregulated STAT3 and ultimately increased PD-L1 expression from the transcription level. The inhibition of miR-411-5p reversed STAT3 and PD-L1 expression inhibited by MIAT knockdown in HCC cells. This study suggests a novel lncRNA-mediated mechanism for HCC cells to evade the immune response; MIAT/miR-411-5p/STAT3/PD-L1 may be a novel therapeutic target for HCC.

Knockdown of lncRNA MIAT attenuated lipopolysaccharide-induced microglial cells injury by sponging miR-613.

Microglia activation and its mediated neuroinflammation play an important role in the pathological process of various central nervous system injuries and diseases. Previous studies have reported abnormal expression of lncRNAs participated in neuroinflammation. However, the expression pattern and involvements of MIAT in neuroinflammatory diseases are not fully investigated. We first screened abnormal expressed lncRNAs in BV2 cells treated with LPS. The expression of MIAT in LPS-induced BV2 cells was detected by qRT-PCR. MTT assay, cell migration, flow cytometry analysis, ELISA, qRT-PCR, and Western blotting analysis were applied to evaluating the effect of si-MIAT on LPS-induced H9C2 cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism of lncRNA-miRNA-mRNA network. The results showed LncRNA MIAT expression was significantly increased in LPS-induced BV2 microglial cells. Besides, MIAT knockdown alleviated LPS-induced repression of cell viability and induction of apoptosis and inflammatory response in BV2 cells. Furthermore, LncRNA MIAT regulated NFAT5 expression via sponging miR-613 in LPS-induced BV2 cells. Altogether, these results suggest that lncRNA MIAT functioned as a ceRNA for miR-613 to modulate NFAT5 expression in LPS-induced BV2 cells, which may contribute to a better understanding of the mechanism of neuroinflammatory diseases.

Long non-coding RNA MIAT is involved in the regulation of pyroptosis in diabetic cardiomyopathy via targeting miR-214-3p

SummaryDiabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as in high-glucose induced cardiomyocytes and diabetic mice. Further, the expression levels of CASP1 and pyroptosis correlation factors (IL-1 and IL-18) were downregulated after silencing MIAT. Through modeling and validation experiments, we then confirmed that the MIAT-miR-214-3p-CASP1 axis serves as an essential point in pyroptosis of DCM mice. These results suggested that silencing MIAT would be a potential treatment strategy for DCM.

LncRNA MIAT Services as a Noninvasive Biomarker for Diagnosis and Correlated with Immune Infiltrates in Breast Cancer.

BackgroundMyocardial infarction associated transcript (MIAT) is identified as a long chain non-coding RNA (lncRNA), which was associated with myocardial infarction susceptibility. While intense efforts have been made to elucidate the relationship between MIAT and carcinogenesis, the tumor immunoreaction of MIAT remains elusive. Thus, this study aimed to investigate the role of MIAT in the immunoregulation of breast cancer (BC) and further explore the better clinical significance.MethodsThe differential expression of MIAT between BC and normal/adjacent tissues was compared using Wilcoxon rank sum test. The diagnostic and prognostic values of elevated MIAT expression in BC tissues were unveiled via receiver operating characteristic (ROC) analysis and KM-plotter analysis. Limma and edgeR package were used to identify differentially expressed genes (DEGs) and microRNAs (DEMs) from TCGA database respectively. A co-expression dataset was constructed to comprehensively understand the relationship between MIAT and DEGs based on the Pearson correlation coefficient. Furthermore, GO and KEGG analyses were conducted to predict the potential functions of MIAT. We next intersected immune-related genes (IRGs) from ImmPort database with MIAT-co-expressed genes to obtain MIAT-co-expressed IRGs, in order to construct MIAT-microRNA (miRNA)-mRNA network. And the correlation between MIAT and tumor-infiltrating immune cells (TICs) and immunophenoscore (IPS) analysis was analyzed by TIMER and CIBERSORT. Finally, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression profiles of MIAT in serum samples.ResultsThe expression levels of MIAT were notably higher in BC than in normal or adjacent tissues. And MIAT expression could be used as a prognostic indicator of mortality risk in patients with BC in different aspects. Moreover, the enrichment analyses suggested that MIAT was strongly involved in BC immune response. In addition, TIMER database and CIBERSORT analyses indicated that MIAT was significantly correlated with 13 types of TICs (B cells, dendritic cells, neutrophils, CD8 T cells, CD4 memory resting T cells, CD4 memory activated T cells, gamma delta T cells, M1 macrophages, plasma cells, activated NK cells, monocytes, M2 macrophages, activated mast cells). Simultaneously, the IPS analysis implied that the higher the MIAT expression, the better the immunotherapy effect. The ROC curve analysis showed that the area under the curve (AUC) value of MIAT was 0.86 (sensitivity = 87.80%, specificity = 75.61%). And the high MIAT expression in serum was positive related to TNM stage (P = 0.032) and lymph node metastasis (P = 0.028).ConclusionMIAT may be a valuable noninvasive diagnostic biomarker for BC and is associated with tumor-infiltrating immune cells in tumor microenvironment, suggesting MIAT as a potential target for future treatment of BC.

LncRNA MIAT regulates autophagy and apoptosis of macrophage infected by Mycobacterium tuberculosis through the miR-665/ULK1 signaling axis

Accumulating lines of evidence have revealed the involvement of long non-coding RNAs (lncRNAs) in the control and elimination of invading Mycobacterium tuberculosis (Mtb) by macrophage. In this study, we sought to elucidate the role of MIAT on autophagy and apoptosis of Mtb-infected macrophage and to reveal the molecular mechanism. We observed that the expression of MIAT was heightened while miR-665 level was declined in THP-1 cells with Bacillus Calmette-Guerin (BCG) infection in a time-dependent manner. Functionally, disruption of MIAT effectively facilitated cell viability and restricted apoptosis ability concomitant with the downregulation of Bax and cleaved caspase-3 along with an accumulation of Bcl-2 in BCG-infected THP-1 cells. Concurrently, the interference of MIAT dramatically disinhibited macrophage autophagy as characterized by diminution of autophagy related markers LC3-II and Beclin-1 as well as increment of p62 in THP-1 cells following BCG infection. Concordantly, depletion of MIAT was found to noticeably aggrandize Mtb survival. Importantly, MIAT served as a ceRNA for sponging miR-665 and negatively regulated its expression. ULK1 was identified as an authentic target of miR-665 and modulated by MIAT. Mechanistically, the functional role of MIAT depletion in macrophage apoptosis and autophagy were tremendously abrogated by the depression of miR-665 and enrichment of ULK1. Overall, the preceding observations clearly illuminated that MIAT was elevated in human macrophage response to BCG infection, and functioned as a negative regulator in autophagy and antimicrobial effects by manipulating miR-665/ULK1 axis during Mtb infection, which may provide a promising target for developing an anti-bacterial against TB.

LncRNA Miat knockdown alleviates endothelial cell injury through regulation of miR-214-3p/Caspase-1 signalling during atherogenesis.

Atherosclerosis is a common problem in healthy people around the world. Long noncoding RNAs (lncRNAs) play important roles in atherosclerosis. Myocardial infarction-associated transcript (Miat) is a cardiovascular disease-associated lncRNA. Its role and mechanism in atherosclerosis is still not fully clarified. Our study aims to explore the role and mechanism of lncRNA Miat in atherosclerosis. The atherosclerosis models were established both in vitro and in vivo. Real-time PCR was used to measure the expression of lncRNA Miat, miR-214, Caspase-1 and IL-1β. Western blot was performed to detect the protein expression of Caspase-1. CCK-8 assay, Tunel staining, and flow cytometry analysis were conducted to detect proliferation and apoptosis of human aortic endothelial cells (HAECs), respectively. Oil red O staining and HE staining were used to evaluated the histological changes of the aorta. The results found that lncRNA Miat was upregulated in ox-LDL-induced atherosclerosis model in vitro. The inhibition of lncRNA Miat protects against ox-LDL-induced HAEC injury, presented as increased cell viability and decreased apoptosis. LncRNA Miat and miR-214has binding site, and CASP1, which encodes Caspase-1, is a target of miR-214. The downregulation of lncRNA Miat increased the expression of miR-214-3p and decreased the expression of Caspase-1, as well as its downstream molecule IL-1β in HAECs. However, the inhibition of miR-214-3p attenuated the effect of lncRNA Miat downregulation on HAECs. Furthermore, the downregulation of lncRNA Miat alleviated atherosclerosis in ApoE-deficient mice. Correspondingly, the expression of miR-214-3p was upregulated and Caspase-1 was downregulated after knockdown of lncRNA Miat. In conclusion, downregulation of lncRNA Miat exerts a protective effect against atherosclerosis through the regulation miR-214-3p/Caspase-1signalling pathway. Therefore, the inhibition of lncRNA Miat expression may be an effective strategy in the treatment of atherosclerosis.

Long non-coding RNA MIAT promotes the proliferation and invasion of laryngeal squamous cell carcinoma cells by sponging microRNA-613.

Accumulating evidence indicates that the long non-coding RNA myocardial infarction associated transcript (lncRNA MIAT) serves an important role in the progression of a number of cancer types. However, the precise molecular mechanism of MIAT in laryngeal squamous cell carcinoma (LSCC) progression remain elusive. The aim of the current study was to assess the effects and to clarify the molecular mechanism of MIAT on the proliferation and invasion of LSCC cells. The expression of MIAT was detected in LSCC tissues and cells using reverse transcription-quantitative PCR. MTT and colony formation assays were performed to examine the effects of MIAT on the proliferation of LSCC cells. Additionally, wound healing and Transwell experiments were employed to examine cellular migration and invasion. Luciferase reporter gene assay was also used to confirm the direct binding between MIAT and microRNA (miR)-613 in LSCC cells. An RNA immunoprecipitation assay was performed to verify the interaction between MIAT and miR-613. In the present study, it was found that the expression of MIAT in LSCC tissues was markedly higher compared with that in adjacent non-tumor tissues. In addition, MIAT expression was also increased in the human LSCC cell lines TU686, TU-177 and AMC-HN-8 compared with that in normal human keratinocytes (HaCaT). Knocking down MIAT expression significantly reduced LSCC cell proliferation and inhibited colony formation, a shown by MTT and colony formation assays, respectively. MIAT knockdown also substantially inhibited the migratory and invasive abilities of LSCC cells, as shown by wound healing and Transwell invasion assays, respectively. Subsequently, luciferase reporter assays verified that MIAT could bind to miR-613, where a negative correlation was observed between the expression of MIAT and miR-613 in LSCC tissues. Suppression of miR-613 partially reversed the inhibitory effects of MIAT knockdown on the proliferation, migration and invasion of LSCC cells. Taken together, the present study identified that MIAT may function as an oncogenic lncRNA to promote LSCC progression, which provides a potential therapeutic target or as a novel diagnostic biomarker for LSCC.

Quercetin Can Inhibit Angiogenesis via the Down Regulation of MALAT1 and MIAT LncRNAs in Human Umbilical Vein Endothelial Cells.

Background:Angiogenesis is an important step in cancer metastasis since it enables the growing tumor to receive nutrients and oxygen. Quercetin is a generic flavonoid and has been investigated for its ability to inhibit angiogenesis in different types of cancers. MALAT1 and MIAT lncRNAs are associated with the angiogenesis process. MALAT1 induces hypoxia-driven angiogenesis via the overexpression of angiogenic genes. Down regulation of MIAT1 could inhibit the proliferation of endothelial cells, tube formation, and migration. In this study, we assessed the anti-angiogenic activity of quercetin on human umbilical vein endothelial cells (HUVEC) via the expression of MALAT1 and MIAT genes.Methods:In the present study, HUVEC cells were incubated with various concentrations of quercetin for 24, 48, and 72 h. Cell proliferation was then evaluated by MTT assay. RNA was extracted by TRIzol and cDNA synthesis. The expression levels of MALAT1 and MIAT genes relative to the GAPDH gene were quantified using the highly sensitive real-time PCR method.Results:Our results demonstrated that quercetin has an inhibitory impact on the cell viability of HUVEC cells. The IC50 values of quercetin after 24, 48, and 72 h were 282.05 μM, 228.25 μM, and 131.65 μM, respectively. The MALAT1/GAPDH ratio was computed as 0.21 for 24h, 0.18 for 48h, and 0.29 for 72 h. The MIAT/GAPDH ratio was computed as 0.82 for 24h, 0.84 for 48h, and 0.78 for 72 h.Conclusions:In conclusion, quercetin treatment had an anti-angiogenic effect on HUVEC cells, at least partially via the down regulation of MALAT1 and MIAT LncRNAs gene expression.

LncRNA MIAT correlates with immune infiltrates and drug reactions in hepatocellular carcinoma

Long non-coding RNA (lncRNA) is a kind of important molecules involved in the formation of immune landscape in tumor microenvironment. However, there are few studies on the relationship between lncRNA and immunomodulatory regulation of hepatocellular carcinoma (HCC). In this study, we combined with single cell transcriptome sequencing and TCGA data to analyze the relationship between lncRNA MIAT and immune cells in HCC. TIMER database analysis indicated that the expression of MIAT in HCC was negatively correlated with tumor purity, positively correlated with the number of immune cells such as B cells, T lymphocytes and macrophages, and positively correlated with the expression of immune checkpoint molecules such as PD-1, PD-L1 and CTLA4. Analysis of single cell sequencing data of immune cells in HCC showed that MIAT was mainly distributed in tumor, and enriched in FOXP3+CD4+T cells and PDCD1+CD8+, GZMK+CD8+T cells, indicating that MIAT may be involved in the immune escape process of HCC. Besides, through the construction of transcription factor (TF) regulatory network, MIAT-TF-mRNA, we found that the interaction of MIAT and TFs may affect the immune microenvironment of LIHC by regulating the expression of target genes JAK2, SLC6A6, KCND1, MEIS3 or RIN1; LncMAP and CARE analysis showed that MIAT was highly related to the sensitivity of many anticancer drugs, especially sorafenib. In addition, the effect of MIAT on PD-L1 and its relationship with sorafinib were verified in clinical specimens and cells. This study made a meaningful attempt to reveal the immune escape mechanism and to find the effectiveness of targeted drugs in patients with HCC.

Identification of a three-long noncoding RNA prognostic model involved competitive endogenous RNA in kidney renal clear cell carcinoma

BackgroundLong noncoding RNA (lncRNA) is generally identified as competing endogenous RNA (ceRNA) that plays a vital role in the pathogenesis of kidney renal clear cell carcinoma (KIRC), the most common subtype of renal cell carcinoma with poor prognosis and unclear pathogenesis. This study established a novel ceRNA network and thus identified a three-lncRNA prognostic model in KIRC patients.MethodsDifferentially expressed genes (DEGs) were screened out from The Cancer Genome Atlas (TCGA) database. The lncATLAS was applied to determine the differentially expressed lncRNAs (DElncRNAs) of the cytoplasm. The miRcode, miRDB, miRTarBase, and TargetScan databases were utilized to predict the interactions of DElncRNAs, DEmiRNAs, and DEmRNAs. Cytoscape was used to construct the ceRNA network. Then, a lncRNA prognostic model (LPM) was constructed based on ceRNA-related lncRNA that was significantly related to overall survival (OS), and its predictive ability was evaluated. Moreover, an LPM-based nomogram model was constructed. The significantly different expression of genes in the LPM was validated in an independent clinical cohort (N = 21) by quantitative RT-PCR.ResultsA novel ceRNA regulatory network, including 73 lncRNAs, 8 miRNAs, and 21 mRNAs was constructed. Functional enrichment analysis indicated that integral components of membrane and PI3K–Akt signaling pathway represented the most significant GO terms and pathway, respectively. The LPM established based on three lncRNAs (MIAT, LINC00460, and LINC00443) of great prognostic value from the ceRNA network was proven to be independent of conventional clinical parameters to differentiate patients with low or high risk of poor survival, with the AUC of 1-, 5- and 10-year OS were 0.723, 0.714 and 0.826 respectively. Furthermore, the nomogram showed a better predictive value in KIRC patients than individual prognostic parameters. The expression of MIAT and LINC00460 was significantly upregulated in the KIRC samples, while the expression of LINC00443 was significantly downregulated compared with the adjacent normal samples in the clinical cohort, TCGA, and GTEx.ConclusionThis LPM based on three-lncRNA could serve as an independent prognostic factor with a tremendous predictive ability for KIRC patients, and the identified novel ceRNA network may provide insight into the prognostic biomarkers and therapeutic targets of KIRC.