ANRIL Overexpression Research Articles

Long noncoding RNA ANRIL alleviates hypoxia-induced pulmonary microvascular endothelial cell damage.

High-altitude pulmonary oedema (HAPE) is a form of noncardiogenic pulmonary oedema. Studies have found that long noncoding RNA (lncRNA) plays an important role in HAPE. ANRIL is significant in pulmonary illnesses, which implies that alterations in ANRIL expression levels may be involved in the beginning and development of HAPE. However, the specific mechanism is indistinct. The present study is meant to explore the effect and mechanism of ANRIL on hypoxic-induced injury of pulmonary microvascular endothelial cells (PMEVCs). In the hypoxic model of PMVECs, overexpression of ANRIL or knockdown of miR-181c-5p was performed to assess cell proliferation, apoptosis, and migration. Furthermore, the levels of apoptosis-related proteins, inflammatory factors, and vascular active factors were also measured. The results showed that, after 24 h of hypoxia, PMVECs proliferation and migration were suppressed in comparison to the control group, along with an increase in apoptosis, a decrease in the expression of ANRIL, and an increase in the expression of miR-181c-5p (all p < .05). The damage caused by hypoxia in PMVECs can be lessened by overexpressing ANRIL, which also inhibits the production of TNF-α, iNOS, and VEGF as well as BAX and cleaved caspase-3 (all p < .05). Further experimental results showed that overexpression of ANRIL and knockdown of miR-181c-5p had the same protection against hypoxic injury in PMVECs (all p < .05). Our study suggests that ANRIL may prevent hypoxia injury to PMVECs in HAPE through the negative regulation of miR-181c-5p.

ANRIL regulates retinoblastoma progression via targeting autophagy by miR-328-3p/TSC1/ULK signaling.

Retinoblastoma is the most common primary intraocular malignancy of childhood. The aim of our study was to investigate the role and regulatory mechanism of the long non-coding RNA ANRIL in retinoblastoma. Here, our data demonstrated that ANRIL overexpression inhibited miR-328-3p expression, but promoted expression of autophagy-related proteins (LC3B, ATG5, and BECN1). Then we predicted the binding sites for ANRIL with miR-328-3p, and for miR-328 3p with TSC1/ULK2 3'-UTR, and confirmed the combination of miR-328-3p and ANRIL and TSC1/ULK2 3'-UTR. Importantly, the data showed that ANRIL overexpression promoted TSC1 and ULK2 expression, and inhibited the phosphorylation of mTOR. Finally, our results indicated that ANRIL overexpression facilitated Y79 cell proliferation and cisplatin-induced apoptosis. Our results indicated that ANRIL promoted the proliferation and cisplatin resistance of Y79 cells through activating autophagy by promoting TSC1/ULK2 ex- pression via acting as a miR-328-3p sponge.

ANRIL promotes the regulation of colorectal cancer on lymphatic endothelial cells via VEGF-C and is the key target for Pien Tze Huang to inhibit cancer metastasis

lncRNA ANRIL is an oncogene, however the role of ANRIL in the regulation of colorectal cancer on human lymphatic endothelial cells (HLECs) is remain elusive. Pien Tze Huang (PZH, PTH) a Tradition Chinese Medicine (TCM) as an adjunctive medication could inhibit the cancer metastasis, however the mechanism still uncovering. We used network pharmacology, subcutaneous and orthotopic transplanted colorectal tumors models to determine the effect of PZH on tumor metastasis. Differential expressions of ANRIL in colorectal cancer cells, and stimulating the regulation of cancer cells on HLECs by culturing HLECs with cancer cells’ supernatants. Network pharmacology, transcriptomics, and rescue experiments were carried out to verify key targets of PZH. We found PZH interfered with 32.2% of disease genes and 76.7% of pathways, and inhibited the growth of colorectal tumors, liver metastasis, and the expression of ANRIL. The overexpression of ANRIL promoted the regulation of cancer cells on HLECs, leading to lymphangiogenesis, via upregulated VEGF-C secretion, and alleviated the effect of PZH on inhibiting the regulation of cancer cells on HLECs. Transcriptomic, network pharmacology and rescue experiments show that PI3K/AKT pathway is the most important pathway for PZH to affect tumor metastasis via ANRIL. In conclusion, PZH inhibits the regulation of colorectal cancer on HLECs to alleviate tumor lymphangiogenesis and metastasis by downregulating ANRIL dependent PI3K/AKT/VEGF-C pathway.

Panax notoginseng saponins inhibits NLRP3 inflammasome-mediated pyroptosis by downregulating lncRNA-ANRIL in cardiorenal syndrome type 4

ObjectiveCardiorenal syndrome type 4 (CRS4) is a complication of chronic kidney disease. Panax notoginseng saponins (PNS) have been confirmed to be efficient in cardiovascular diseases. Our study aimed to explore the therapeutic role and mechanism of PNS in CRS4.MethodsCRS4 model rats and hypoxia-induced cardiomyocytes were treated with PNS, with and without pyroptosis inhibitor VX765 and ANRIL overexpression plasmids. Cardiac function and cardiorenal function biomarkers levels were measured by echocardiography and ELISA, respectively. Cardiac fibrosis was detected by Masson staining. Cell viability was determined by cell counting kit-8 and flow cytometry. Expression of fibrosis-related genes (COL-I, COL-III, TGF-β, α-SMA) and ANRIL was examined using RT-qPCR. Pyroptosis-related protein levels of NLRP3, ASC, IL-1β, TGF-β1, GSDMD-N, and caspase-1 were measured by western blotting or immunofluorescence staining.ResultsPNS improved cardiac function, and inhibited cardiac fibrosis and pyroptosis in a dose-dependent manner in model rats and injured H9c2 cells (p < 0.01). The expression of fibrosis-related genes (COL-I, COL-III, TGF-β, α-SMA) and pyroptosis-related proteins (NLRP3, ASC, IL-1β, TGF-β1, GSDMD-N, and caspase-1) was inhibited by PNS in injured cardiac tissues and cells (p < 0.01). Additionally, ANRIL was upregulated in model rats and injured cells, but PNS reduced its expression in a dose-dependent manner (p < 0.05). Additionally, the inhibitory effect of PNS on pyroptosis in injured H9c2 cells was enhanced by VX765 and reversed by ANRIL overexpression, respectively (p < 0.05).ConclusionPNS inhibits pyroptosis by downregulating lncRNA-ANRIL in CRS4.

LncRNA ANRIL promotes HR repair through regulating PARP1 expression by sponging miR-7-5p in lung cancer

BackgroundRadiotherapy is an important treatment for lung cancer, mainly by triggering DNA double-strand breaks to induce cell death. Blocking DNA damage repair can increase the radiosensitivity of tumor cells. Recent studies have identified long noncoding RNAs as key regulators in DNA damage repair. The lncRNA ANRIL was previously shown to be involved in homologous recombination (HR) repair, but its specific mechanism has not been fully elucidated.MethodsThe downstream interacting miRNAs of ANRIL were predicted according to miRanda software. Fluorescence quantitative PCR was used to detect the expression levels of ANRIL and candidate miRNAs. Clone formation experiment and cell viability assays detect cell viability after ionizing radiation. Apoptosis assay was used to detect the apoptosis of cells after 8 h of ionizing radiation. Western blot analysis and immunofluorescence assays verified the protein expression levels of the downstream target molecule PARP1 of miR-7-5p and key molecules in the HR pathway. Fluorescent reporter gene experiments were used to verify the interaction between ANRIL and miR-7-5p and between miR-7-5p and PARP1.ResultsBioinformatics analysis and qPCR validation suggested that miR-7-5p might be a downstream molecule of ANRIL. The expression of miR-7-5p was up-regulated after knockdown of ANRIL, and the expression of miR-7-5p was down-regulated after overexpression of ANRIL. Meanwhile, there was a negative correlation between ANRIL and miR-7-5p expression changes before and after ionizing radiation. The luciferase reporter gene assay confirmed the existence of ANRIL binding site with miR-7-5p, and found that transfection of miR-7-5p inhibitor can reduce the radiation sensitivity of ANRIL-KD cells. A downstream target molecule of miR-7-5p related to HR repair, PARP1, was screened through website prediction. Subsequently, it was confirmed by Western blot and luciferase reporter assays that miR-7-5p could down-regulate the expression of PARP1, and there was a miR-7-5p binding site on the 3'UTR of PARP1 mRNA. This suggests that ANRIL may act as a competitive endogenous RNA to bind miR-7-5p and upregulate the expression of PARP1. Western blot and immunofluorescence staining were used to detect the expression changes of HR repair factors in ANRIL-KD cells after ionizing radiation, and it was found that knockdown of ANRIL can inhibit the expression of PARP1, BRCA1 and Rad51, hinder radiation-induced HR repair, and eventually result in resensitizing ANRIL-KD cells to ionizing radiation.ConclusionsOur findings provide evidence that ANRIL targets the miR-7-5p/PARP1 axis to exert its regulatory effect on HR repair, suggesting that altering ANRIL expression may be a promising strategy to overcome radiation resistance.

ANRIL overexpression globally induces expression and alternative splicing of genes involved in inflammation in HUVECs.

Long non‑coding (lnc)RNAs serve important cellular functions and certain lncRNAs have roles in different mechanisms of gene regulation. lncRNA‑antisense non‑coding RNA in the INK4 locus (ANRIL) affects cell inflammation; however, the potential genes underlying the inflammatory response regulated by ANRIL remain unclear. In the present study, the potential function of ANRIL in regulating gene expression and alternative splicing was assessed. ANRIL‑regulated human umbilical vein endothelial cell (HUVEC) transcriptome was obtained using high‑throughput RNA sequencing (RNA‑seq) to evaluate the potential role of ANRIL. Following plasmid transfection, gene expression profile and alternative splicing pattern of HUVECs overexpressing ANRIL were analyzed using RNA‑seq. ANRIL overexpression affected the transcription levels of genes associated with the inflammatory response, NF‑κB signaling pathway, typeI interferon‑mediated signal transduction pathway and innate immune response. ANRIL regulated the alternative splicing of hundreds of genes with functions such as gene expression, translation, DNA repair, RNA processing and participation in the NF‑κB signaling pathway. Many of these genes serve a key role in the inflammatory response. ANRIL‑regulated inflammatory response may be achieved by regulating alternate splicing and transcription. The present study broadened the understanding of ANRIL‑mediated gene regulation mechanisms and clarified the role of ANRIL in mediating inflammatory response mechanisms.

Long Non-Coding RNA ANRIL as a Potential Biomarker of Chemosensitivity and Clinical Outcomes in Osteosarcoma.

Simple SummaryOsteosarcoma is a bone cancer with a poor prognosis. This is, in part, due to resistance to current standard-of-care chemotherapeutic treatment. As personalized treatment plans become more widely utilized, the role of patient-specific genome markers may serve to identify individuals with chemo-resistant disease at the outset of diagnosis. ANRIL, a long non-coding RNA, has promise as a predictive biomarker. Utilizing osteosarcoma cell lines, we observed that altering the expression of ANRIL significantly alters the sensitivity to cisplatin and doxorubicin, two agents that are a standard-of-care for treatment. Analysis of clinical data from the TARGET dataset confirmed higher ANRIL expression portending poorer prognosis, as evidenced by association with death and metastases at diagnosis.Osteosarcoma has a poor prognosis due to chemo-resistance and/or metastases. Increasing evidence shows that long non-coding RNAs (lncRNAs) can play an important role in drug sensitivity and cancer metastasis. Using osteosarcoma cell lines, we identified a positive correlation between the expression of a lncRNA and ANRIL, and resistance to two of the three standard-of-care agents for treating osteosarcoma—cisplatin and doxorubicin. To confirm the potential role of ANRIL in chemosensitivity, we independently inhibited and over-expressed ANRIL in osteosarcoma cell lines followed by treatment with either cisplatin or doxorubicin. Knocking-down ANRIL in SAOS2 resulted in a significant increase in cellular sensitivity to both cisplatin and doxorubicin, while the over-expression of ANRIL in both HOS and U2OS cells led to an increased resistance to both agents. To investigate the clinical significance of ANRIL in osteosarcoma, we assessed ANRIL expression in relation to clinical phenotypes using the osteosarcoma data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset. Higher ANRIL expression was significantly associated with increased rates of metastases at diagnosis and death and was a significant predictor of reduced overall survival rate. Collectively, our results suggest that the lncRNA ANRIL can be a chemosensitivity and prognosis biomarker in osteosarcoma. Furthermore, reducing ANRIL expression may be a therapeutic strategy to overcome current standard-of-care treatment resistance.

Puerarin protects cardiomyocytes from ischemia-reperfusion injury by upregulating LncRNA ANRIL and inhibiting autophagy.

This study analyzed the roles of puerarin and LncRNA ANRIL in myocardial ischemia-reperfusion injury. Hypoxia/reperfusion (H/R) model was established with H9C2 cells. Effects of puerarin of gradient concentrations on cardiomyocytes at different time points of hypoxia and reoxygenation were detected by quantitative real-time polymerase chain reaction (qRT-PCR), cell counting kit-8 (CCK-8), and microscope observation. Effects of puerarin on cardiomyocyte viability, ANRIL expression, contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA), apoptosis, and expressions of autophagy-related genes after H/R injury were determined by CCK-8, quantitative real-time polymerase chain reaction (qRT-PCR), ELISA, flow cytometry, and Western blot, respectively. After cell transfection, the effects of overexpressed and knockdown of ANRIL on cardiomyocytes and H/R-injured cardiomyocytes were examined by rescue experiments. The ischemia-reperfusion (I/R)-injured rat model was established to examine the protective effect of puerarin in vivo. Prolonged hypoxia downregulated ANRIL expression in cardiomyocytes and reduced cardiomyocyte viability. Prolonged reoxygenation increased apoptosis. Both cardiomyocyte viability and ANRIL expression showed a dose-dependent relationship with puerarin. Puerarin reversed the effects of H/R injury on cardiomyocyte viability, ANRIL expression, contents of LDH and MDA, apoptosis, and expressions of autophagy-related genes. Overexpression and knockdown of ANRIL regulated the functions of cardiomyocytes and the expressions of autophagy-related genes. Puerarin reversed the effects of knockdown of ANRIL on H/R-injured cells. The results of In vivo experiments confirmed that puerarin protected myocardial tissues by up-regulating ANRIL and inhibiting autophagy.

Sevoflurane Represses Proliferation and Migration of Glioma Cells by Regulating the ANRIL/let-7b-5p Axis.

Background: Glioma is a malignant brain tumor with poor prognosis. Sevoflurane has been shown to have antitumor effects in various cancers. However, the underlying role and mechanism of sevoflurane in glioma is still unclear. Materials and Methods: Glioma cell lines were exposed different concentrations of sevoflurane (sev). The cell proliferation and migration were examined by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. All protein levels were measured by Western blot. The levels of noncoding RNA in the INK4 locus (ANRIL) and let-7b-5p were detected by quantitative real-time polymerase chain reaction. The binding sites between ANRIL and let-7b-5p were predicted by StarBase v.3.0 and confirmed using dual-luciferase reporter assay. Results: Sevoflurane treatment suppressed proliferation and migration of glioma cells. The expression of ANRIL was downregulated in glioma cells after treatment with sevoflurane in a dose-dependent manner, and overexpression of ANRIL reversed sevoflurane-induced inhibition of proliferation and migration of glioma cells. Furthermore, let-7b-5p was targeted by ANRIL, and ANRIL knockdown recovered the promoting effects of silencing let-7b-5p on proliferation, migration, and JAK2/STAT3 pathway in sevoflurane-treated glioma cells. Conclusions: Sevoflurane hindered proliferation and migration through JAK2/STAT3 pathway mediated by ANRIL and let-7b-5p in glioma cells, indicating a new reference for the application of anesthetics like sevoflurane in glioma.

Knockdown of lncRNA ANRIL inhibits the development of cisplatin resistance by upregulating miR‑98 in lung cancer cells.

Emerging evidence has demonstrated that abnormally expressed long non‑coding (lnc) RNAs contribute to drug resistance in various types of malignancy. LncRNA antisense non‑coding RNA in the inhibitor of cyclin‑dependent kinase 4 locus (ANRIL) exerts oncogenic activity and acts as a key player in a variety of carcinomas, including non‑small cell lung cancer. The present study aimed to investigate the functional roles of ANRIL in cisplatin (DDP) resistance of lung cancer and the underlying mechanism involved in the competing endogenous RNA regulatory network. The expression levels of ANRIL and microRNA (miR)‑98 in lung cancer tissues and DDP‑resistant lung cancer cells were assessed by reverse transcription‑quantitative (RT‑q) PCR. The Pearson's correlation coefficient was used to determine the correlation between the expression levels of ANRIL and miR‑98 in lung cancer tissues. Cell proliferation and apoptosis were detected by MTT assay and flow cytometry analysis, respectively. The expression levels of proliferation‑ and apoptosis‑associated proteins were detected by western blot analysis. The potential interaction between ANRIL and miR‑98 was confirmed by RNA immunoprecipitation (RIP), dual luciferase reporter assay and RT‑qPCR. The results of the present study demonstrated that ANRIL was upregulated and miR‑98 was downregulated in lung cancer tissues and A549/DDP cells. In addition, the Pearson's correlation analysis revealed that the expression of ANRIL was significantly negatively correlated with that of miR‑98 in lung cancer tissues. ANRIL overexpression reversed the DDP‑induced cell proliferation suppression and apoptosis in lung cancer cells, whereas ANRIL knockdown exhibited the opposite effects. RIP, dual luciferase reporter assay and RT‑qPCR analysis results demonstrated that ANRIL directly interacted with miR‑98 and suppressed miR‑98 expression. Furthermore, transfection with the miR‑98 mimics promoted DDP‑induced cell proliferation inhibition and apoptosis in lung cancer cells, and these effects were partially reversed by ANRIL overexpression. In conclusion, ANRIL knockdown inhibited the development of DDP resistance by upregulating miR‑98, providing novel insights into the molecular mechanism of ANRIL involvement in DDP resistance of lung cancer cells.

Silencing of circular RNA ANRIL attenuates oxygen\u2013glucose deprivation and reoxygenation-induced injury in human brain microvascular endothelial cells by sponging miR-622

BackgroundCircular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia–reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen–glucose deprivation and reoxygenation (OGD/R)-induced cell injury.ResultsThe expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor.ConclusionsKnockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

Long non-coding RNA ANRIL alleviates H2O2-induced injury by up-regulating microRNA-21 in human lens epithelial cells.

The accurate role of ANRIL in cataract is poorly understood. We aimed to reveal the effects of ANRIL on H2O2-treated HLECs, SRA01/04, as well as the regulatory mechanisms. Oxidative stress model of HLECs was induced by H2O2. Cell injury was evaluated according to cell proliferation, apoptosis and DNA damage using CCK-8 assay/flow cytometry and TUNEL assays/γH2AX staining. Expressions of ANRIL and miR-21 in HLECs were determined by RT-qPCR. The effects of miR-21, miR-34a and miR-122-5p inhibition as well as AMPK and β-catenin on HLECs with ANRIL overexpression and H2O2 stimulation were analyzed. In vivo experiment was performed via RT-qPCR. H2O2 repressed proliferation and induced apoptosis or DNA damage in HLECs. Those alterations induced by H2O2 were attenuated by ANRIL overexpression. MiR-21 was positively regulated by ANRIL, and both of them were repressed in H2O2-induced HLECs and cataract patient tissues. Inhibition of miR-21 but not miR-34a or miR-122-5p reversed the effects of ANRIL on H2O2-treated HLECs. Phosphorylation of AMPK and expression of β-catenin were increased by ANRIL via regulating miR-21. AMPK and β-catenin affected beneficial function of ANRIL-miR-21 axis.Therefore, lncRNA ANRIL attenuated H2O2-induced cell injury in HELCs via up-regulating miR-21 via the activation of AMPK and β-catenin.

LncRNA MALAT1 Promotes Ulcerative Colitis by Upregulating lncRNA ANRIL.

LncRNA MALAT1 contributes to the inflammatory responses induced by lipopolysaccharides (LPS), which shares similar pathogenesis with ulcerative colitis (UC), indicating the potential involvement of MALAT1 in UC. Expression of MALAT1 and lncRNA ANRIL in both UC patients and healthy controls was analyzed by RT-qPCR. ROC curve analysis was used to evaluate the diagnostic value of MALAT1 for UC. Cell transfections were performed to analyze the interactions between MALAT1 and ANRIL. Cell apoptosis was analyzed by cell apoptosis assay. In the present study, we found that MALAT1 was upregulated in colonic mucosa tissues of UC patients in comparison with healthy controls. Plasma levels of MALAT1 were also higher in UC patients than in healthy controls, and upregulation of plasma MALAT1 distinguished UC patients from healthy controls. ANRIL was also upregulated in colonic mucosa tissues of UC patients than in that of healthy controls. ANRIL and MALAT1 were significantly and positively correlated in UC patients but not in healthy controls. Normal colonic epithelial cells with ANRIL overexpression showed no significantly changed MALAT1 overexpression, while MALAT1 overexpression led to promoted ANRIL expression. MALAT1 and ANRIL overexpression led to promoted apoptosis of FHCs. MALAT1 promotes ulcerative colitis by upregulating ANRIL.

LncRNA ANRIL Ameliorates Oxygen and Glucose Deprivation (OGD) Induced Injury in Neuron Cells via miR-199a-5p/CAV-1 Axis.

Ischemia stroke is one of the leading causes of death and disability in the world. Long non-coding RNA ANRIL has been reported to play an important role in ischemic injury. In this study, we aim to explore the mechanism by which ANRIL exhibits protective effect. Middle cerebral artery occlusion mouse models were applied and infarction areas were assessed by TTC assay. The expression of ANRIL and miR-199a-5p were determined by qPCR. Oxygen and glucose deprivation treatment was applied to mimic in vitro ischemia injury in N-2a cells. The levels of BCL-2, BAX, MEK, ERK, CAV-1 were determined by western blot. Cell viability were assessed by MTT assay. The direct interaction among miR-199a-5p and ANRIL, miR-199a-5p and CAV-1 were demonstrated by dual Luciferase report assay. ANRIL and miR-199a-5p expression were changed in both in vivo and in vitro ischemia model. Overexpression of ANRIL or inhibition of miR-199a-5p could protect cells against ischemia induced injury by elevating cell viability through CAV-1 mediated MEK/ERK pathway. miR-199a-5p attenuated CAV-1 expression by direct targeting. ANRIL competitively interacted with miR-199a-5p in N-2a cells, leading to a de-repression of CAV-1. ANRIL protects N-2a cells against ischemia induced injury by elevated CAV-1 by competitively interacting with miR-199a-5p, thus activating MEK/ERK pathway and elevating cell viability.

Expression of Concern: Overexpression of lncRNA ANRIL aggravated hydrogen peroxide-disposed injury in PC-12 cells via inhibiting miR-499a/PDCD4 axis-mediated PI3K/AKT/mTOR/p70S6K pathway

This article refers to:RETRACTED ARTICLE: Overexpression of lncRNA ANRIL aggravated hydrogen peroxide-disposed injury in PC-12 cells via inhibiting miR-499a/PDCD4 axis-mediated PI3K/Akt/mTOR/p70S6K pathway

Statement of Retraction

This article refers to:RETRACTED ARTICLE: Overexpression of lncRNA ANRIL aggravated hydrogen peroxide-disposed injury in PC-12 cells via inhibiting miR-499a/PDCD4 axis-mediated PI3K/Akt/mTOR/p70S6K pathway

The Long Noncoding RNA ANRIL Promotes Cell Apoptosis in Lipopolysaccharide-Induced Acute Kidney Injury Mediated by the TLR4/Nuclear Factor-Kappa B Pathway

Background/Aims: The purpose of this study is to analyze the expression and biological function of lncRNA ANRIL, microRNA-199a, TLR4, and nuclear factor-kappa B (NF-κB) in acute renal injury (AKI) induced by lipopolysaccharide (LPS). Methods: The levels of ANRIL and microRNA-199a in mouse cells and kidneys were detected by quantitative-polymerase chain reaction. Western blot analysis was used for the NF-κB pathway protein. MTT assay was used for cell viability. Enzyme-linked immunosorbent assay was used for the secretion of inflammatory factors in mouse kidney tissue. Apoptosis was measured by flow cytometry and Western blotting. The potential binding region between ANRIL and miR-199a was verified by luciferase reporter assay. Results: The upregulation of ANRIL can reduce the expression of microRNA-199a and increases the number of apoptotic cells. The expression levels of ANRIL in LPS-induced AKI mice and LPS-treated HK2 cells were upregulated compared with the control group. Overexpression of ANRIL increased apoptosis and promoted TLR4 (Toll-like receptor 4), NF-κB phosphorylation, and downstream transcription factor production. Conclusion: ANRIL/NF-κB pathway in LPS-induced apoptosis provided theoretical guidance for ANRIL in the treatment of AKI.

Expression and function of lncRNA ANRIL in a mouse model of acute myocardial infarction combined with type 2 diabetes mellitus

BackgroundThis study intends to explore whether lncRNA ANRIL has an influence on type 2 diabetes mellitus (T2DM) complicated with acute myocardial infarction (MI) and to further investigate the underlying mechanism. MethodsThe ANRIL level in peripheral blood from patients was detected by qRT-PCR. A T2DM mouse model was established by intraperitoneal injection of streptozocin (STZ). MI was induced by ligation of the left anterior descending coronary artery. Cardiac function parameters were measured using echocardiography. Triphenyltetrazolium chloride (TTC) staining was performed to determine the infarct size, and Masson staining was conducted to delineate the area of fibrosis in the myocardium. TUNEL staining was used to detect myocardial cell apoptosis. The expression of the myocardial fibrosis-related proteins TGF-β1, collagen I and collagen III was analysed using Western blot. ResultsANRIL was upregulated in peripheral venous blood from patients with T2DM-MI and in myocardial tissues from the established T2DM-MI model mice. Furthermore, ANRIL overexpression caused cardiac dysfunction and increased the heart/body weight rate and infarct size in the T2DM-MI mice. Moreover, ANRIL overexpression caused myocardial fibrosis and myocardial cell apoptosis, and it increased the expression of the myocardial fibrosis-related proteins TGF-β1, collagen I and collagen III in the T2DM-MI mice. However, ANRIL knockdown exerted the opposite effects. ConclusionANRIL may be involved in the progression and development of T2DM-MI, which might provide novel ideas for the prevention and treatment of cardiovascular diseases.

Expression and function of lncRNA ANRIL in a mouse model of acute myocardial infarction combined with type 2 diabetes mellitus.

This study intends to explore whether lncRNA ANRIL has an influence on type 2 diabetes mellitus (T2DM) complicated with acute myocardial infarction (MI) and to further investigate the underlying mechanism. The ANRIL level in peripheral blood from patients was detected by qRT-PCR. A T2DM mouse model was established by intraperitoneal injection of streptozocin (STZ). MI was induced by ligation of the left anterior descending coronary artery. Cardiac function parameters were measured using echocardiography. Triphenyltetrazolium chloride (TTC) staining was performed to determine the infarct size, and Masson staining was conducted to delineate the area of fibrosis in the myocardium. TUNEL staining was used to detect myocardial cell apoptosis. The expression of the myocardial fibrosis-related proteins TGF-β1, collagen I and collagen III was analysed using Western blot. ANRIL was upregulated in peripheral venous blood from patients with T2DM-MI and in myocardial tissues from the established T2DM-MI model mice. Furthermore, ANRIL overexpression caused cardiac dysfunction and increased the heart/body weight rate and infarct size in the T2DM-MI mice. Moreover, ANRIL overexpression caused myocardial fibrosis and myocardial cell apoptosis, and it increased the expression of the myocardial fibrosis-related proteins TGF-β1, collagen I and collagen III in the T2DM-MI mice. However, ANRIL knockdown exerted the opposite effects. ANRIL may be involved in the progression and development of T2DM-MI, which might provide novel ideas for the prevention and treatment of cardiovascular diseases.

RETRACTED ARTICLE: Overexpression of lncRNA ANRIL aggravated hydrogen peroxide-disposed injury in PC-12 cells via inhibiting miR-499a/PDCD4 axis-mediated PI3K/Akt/mTOR/p70S6K pathway

We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article: Zhiliang Guo, Lanlan Li, Yu Gao, Xiaoyun Zhang and Min Cheng. (2019). Overexpression of lncRNA ANRIL aggravated hydrogen peroxide-disposed injury in PC-12 cells via inhibiting miR-499a/PDCD4 axis-mediated PI3K/Akt/mTOR/p70S6K pathway. Artificial Cells, Nanomedicine, and Biotechnology. 47:1, 2624–2633. DOI: 10.1080/21691401.2019.1629953 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors checked their data and confirmed there are fundamental errors present. Therefore, they have agreed to the retraction of this article. The authors apologise for this oversight. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.