Epimedium-Curculigo herb pair enhances bone repair with infected bone defects and regulates osteoblasts through LncRNA MALAT1/miR-34a-5p/SMAD2 axis.

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-ß signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-ß/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.

Suppression of lncRNA-MALAT1 activity ameliorates femoral head necrosis by modulating mTOR signaling.

Introduction: Avascular necrosis of the femoral head (ANFH) is one of the most complicated bone disorders; management remains challenging. We evaluated the effect of lncRNA-MALAT1 suppression on ANFH rats. Material and methods: Dexamethasone was injected intravenously at 0.5 mg/kg daily for 30 days to induce ANFH; an lncRNA-MALAT1 inhibitor group received the inhibitor for the entire 30 days. LncRNA-MALAT1 suppression was evaluated by measuring blood hexosamine and hydroxyproline levels, and that of circulating endothelial progenitor cells (EPCs). Changes in femoral head bone ultrastructure were assessed via transmission electron microscopy and magnetic resonance imaging (MRI). We used reverse transcription polymerase chain reaction (RT-PCR) and Western blotting to measure gene and protein expression levels in femoral head tissue. Results: The blood hexosamine level rose and that of hydroxyproline fell in the LncRNA-MALAT1 inhibitor group compared to the ANFH group. LncRNA-MALAT1 suppression increased the level of circulating EPCs. Ultrastructural changes in the femoral bone head were alleviated by the lncRNA-MALAT1 inhibitor. LncRNA-MALAT1 suppression lowered the levels of AMPK, mTOR, and Beclin-1 in rat tissue homogenates. Conclusions: LncRNA-MALAT1 suppression attenuated dexamethasone-induced femoral head necrosis by regulating AMPK/mTOR/Beclin-1 signaling.

The lncRNA-MALAT1/miR-330-3p Axis Promotes Growth and Metastasis of Gastric Cancer Through Regulation of Vascular Endothelial Growth Factor A: A Genetic and Cell Evaluation Study

SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.

Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.

Lentinus edodes mycelium polysaccharide inhibits AGEs-induced HUVECs pyroptosis by regulating LncRNA MALAT1/miR-199b/mTOR axis and NLRP3/Caspase-1/GSDMD pathway.

A novel Lentinus edodes mycelia polysaccharide (LMP) prepared in our laboratory has been identified to be effective in inhibiting the damage of islet ß cells induced by glucose toxicity. However, whether it can effectively alleviate the pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by advanced glycation end products (AGEs) remains unclear. Bioinformatics and cell biology techniques were used to explore the mechanism of LMP inhibiting AGEs-induced HUVECs damage. The results indicated that AGEs significantly increased the expression of LncRNA MALAT1, decreased cell viability to 79.67 %, increased intracellular ROS level to 248.19 % compared with the control group, which further led to cell membrane rupture. The release of LDH in cellular supernatant was increased to 149.42 %, and the rate of propidium iodide staining positive cells increased to 277.19 %, indicating the cell pyroptosis occurred. However, the above trend was effectively retrieved after the treatment with LMP. LMP effectively decreased the expression of LncRNA MALAT1 and mTOR, promoted the expression of miR-199b, inhibited AGEs-induced HUVECs pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway. LncRNA MALAT1 might be a new target for LMP to inhibit AGEs-induced HUVECs pyroptosis. This study manifested the role of LMP in improving diabetes angiopathy and broadens the application of polysaccharide.

Long noncoding RNA MALAT-1: A versatile regulator in cancer progression, metastasis, immunity, and therapeutic resistance.

Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that do not code for proteins but have been linked to cancer development and metastasis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) influences crucial cancer hallmarks through intricate molecular mechanisms, including proliferation, invasion, angiogenesis, apoptosis, and the epithelial-mesenchymal transition (EMT). The current article highlights the involvement of MALAT-1 in drug resistance, making it a potential target to overcome chemotherapy refractoriness. It discusses the impact of MALAT-1 on immunomodulatory molecules, such as major histocompatibility complex (MHC) proteins and PD-L1, leading to immune evasion and hindering anti-tumor immune responses. MALAT-1 also plays a significant role in cancer immunology by regulating diverse immune cell populations. In summary, MALAT-1 is a versatile cancer regulator, influencing tumorigenesis, chemoresistance, and immunotherapy responses. Understanding its precise molecular mechanisms is crucial for developing targeted therapies, and therapeutic strategies targeting MALAT-1 show promise for improving cancer treatment outcomes. However, further research is needed to fully uncover the role of MALAT-1 in cancer biology and translate these findings into clinical applications.

LncRNA MALAT1 in Keratinocyte function: A review of recent advances.

Keratinocytes, the principal epidermal cells, play a vital role in maintaining the structural integrity and functionality of the skin. Beyond their protective role, keratinocytes are key contributors to the process of wound healing, as they migrate to injury sites, proliferate, and generate new layers of epidermis, facilitating tissue repair and remodeling. Moreover, keratinocytes actively participate in the skin's immune responses, expressing pattern recognition receptors (PRRs) to detect microbial components and interact with immune cells to influence adaptive immunity. Keratinocytes express a diverse repertoire of signaling pathways, transcription factors, and epigenetic regulators to regulate their growth, differentiation, and response to environmental cues. Among these regulatory elements, long non-coding RNAs (lncRNAs) have emerged as essential players in keratinocyte biology. LncRNAs, including MALAT1, play diverse roles in gene regulation and cellular processes, influencing keratinocyte proliferation, differentiation, migration, and response to environmental stimuli. Dysregulation of specific lncRNAs such as MALAT1 can disrupt keratinocyte homeostasis, leading to impaired differentiation, compromised barrier integrity, and contributing to the pathogenesis of various skin disorders. Understanding the intricate interplay between lncRNAs and keratinocytes offers promising insights into the molecular underpinnings of skin health and disease, with potential implications for targeted therapies and advancements in dermatological research. Hence, our objective is to provide a comprehensive summary of the available knowledge concerning keratinocytes and their intricate relationship with MALAT1.

Expression and diagnostic value of lncRNA MALAT1 and NLRP3 in lower limb atherosclerosis in diabetes.

OBJECTIVE: This study aimed to examine the diagnostic predictive value of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1(MALAT1) and NOD-like receptor protein 3(NLRP3) expression in patients with type 2 diabetes mellitus(T2DM) and lower extremity atherosclerosis disease (LEAD). METHODS: A total of 162 T2DM patients were divided into T2DM with LEAD group (T2DM + LEAD group) and T2DM alone group (T2DM group). The lncRNA MALAT1 and NLRP3 expression levels were measured in peripheral blood, and their correlation was examined. Least absolute shrinkage and selection operator (LASSO) regression model was used to screen for the best predictors of LEAD, and multivariate logistic regression was used to establish a predictive model and construct the nomogram. The effectiveness of the nomogram was assessed using the receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: The levels of the lncRNA MALAT1 and NLRP3 in the T2DM + LEAD group were significantly greater than those in the T2DM group (P <0.001), and the level of the lncRNA MALAT1 was positively correlated with that of NLRP3 (r = 0.453, P<0.001). The results of the LASSO combined with the logistic regression analysis showed that age, smoking, systolic blood pressure (SBP), NLRP3, and MALAT1 were the influencing factors of T2DM with LEAD(P<0.05). ROC curve analysis comparison: The discriminatory ability of the model (AUC = 0.898), MALAT1 (AUC = 0.804), and NLRP3 (AUC = 0.794) was greater than that of the other indicators, and the predictive value of the model was the greatest. Calibration curve: The nomogram model was consistent in predicting the occurrence of LEAD in patients with T2DM (Cindex = 0.898). Decision curve: The net benefit rates obtained from using the predictive models for clinical intervention decision-making were greater than those obtained from using the individual factors within the model. CONCLUSION: MALAT1 and NLRP3 expression increased significantly in T2DM patients with LEAD, while revealing the correlation between MALAT1 and NLRP3. The lncRNA MALAT1 was found as a potential biomarker for T2DM with LEAD.

The mechanism of lncRNA MALAT1 targeting the miR-124-3p/IGF2BP1 axis to regulate osteogenic differentiation of periodontal ligament stem cells.

OBJECTIVES: This study aimed to investigate the regulatory roles of lncRNA MALAT1, miR-124-3p, and IGF2BP1 in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). MATERIALS AND METHODS: We characterized PDLSCs by employing quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses to evaluate the expression of key osteogenic markers including ALPL, SPP1, and RUNX2. Manipulation of lncRNA MALAT1 and miR-124-3p expression levels was achieved through transfection techniques. In addition, early osteogenic differentiation was assessed via Alkaline phosphatase (ALP) staining, and mineral deposition was quantified using Alizarin Red S (ARS) staining. Cellular localization of lncRNA MALAT1 was determined through Fluorescence In Situ Hybridization (FISH). To elucidate the intricate regulatory network, we conducted dual-luciferase reporter assays to decipher the binding interactions between lncRNA MALAT1 and miR-124-3P as well as between miR-124-3P and IGF2BP1. RESULTS: Overexpression of lncRNA MALAT1 robustly promoted osteogenesis in PDLSCs, while its knockdown significantly inhibited the process. We confirmed the direct interaction between miR-124-3p and lncRNA MALAT1, underscoring its role in impeding osteogenic differentiation. Notably, IGF2BP1 was identified as a direct binding partner of lncRNA MALAT1, highlighting its pivotal role within this intricate network. Moreover, we determined the optimal IGF2BP1 concentration (50 ng/ml) as a potent enhancer of osteogenesis, effectively countering the inhibition induced by si-MALAT1. Furthermore, in vivo experiments utilizing rat calvarial defects provided compelling evidence, solidifying lncRNA MALAT1's crucial role in bone formation. CONCLUSIONS: Our study reveals the regulatory network involving lncRNA MALAT1, miR-124-3p, and IGF2BP1 in PDLSCs' osteogenic differentiation. CLINICAL RELEVANCE: These findings enhance our understanding of lncRNA-mediated osteogenesis, offering potential therapeutic implications for periodontal tissue regeneration and the treatment of bone defects.

Long Non-Coding RNA MALAT1 Protects Against Spinal Cord Injury via Suppressing microRNA-125b-5p Mediated Microglial M1 Polarization, Neuroinflammation, and Neural Apoptosis.

Our previous studies have discovered that long non-coding RNA (lncRNA) MALAT1 and its target microRNA-125b-5p (miR-125b-5p) are implicated in neurological diseases via regulating neuroinflammation and neuronal injury. This study aimed to further explore the relationship between lncRNA MALAT1 and miR-125b-5p, as well as their effect on microglial activation, neuroinflammation, and neural apoptosis in spinal cord injury (SCI). Primary microglia from Sprague Dawley rats were stimulated with lipopolysaccharide (LPS). Then, microglia were transfected with lncRNA MALAT1 overexpression or knock-down adenovirus-associated virus with or without miR-125b-5p mimic. The culture medium of microglia was incubated with primary neurons. SCI rats were established for in vivo validation. LncRNA MALAT1 expression was reduced by LPS treatment in a dose-dependent manner. LncRNA MALAT1 overexpression suppressed the microglial M1 polarization (decreased iNOS but increased ARG1), neuroinflammation (declined PTGS2, TNF-α, IL-1ß, and IL-6), and microglia-induced neural apoptosis (lower TUNEL positive cells and C-caspase3 but higher BCL2) under LPS treatment; its knock-down displayed the opposite trend. Moreover, lncRNA MALAT1 directly bound to and negatively regulated miR-125b-5p. MiR-125b-5p mimic promoted microglial M1 polarization, neuroinflammation, and microglia-induced neural apoptosis following LPS treatment; also, it could attenuate the effect of lncRNA MALAT1. Further in vivo study displayed that lncRNA MALAT1 overexpression elevated the Basso-Beattie-Bresnahan motor function score and improved neural injury. Also, in vivo validation indicated a similar effect of lncRNA MALAT1 on microglial polarization and neuroinflammation as in vitro. LncRNA MALAT1 improves SCI recovery via miR-125b-5p mediated microglial M1 polarization, neuroinflammation, and neural apoptosis.

CD95 promotes stemness of colorectal cancer cells by lncRNA MALAT1.

Colorectal cancer (CRC) is the second most fatal cancer. Many studies have shown that cancer stemness contributes to resistance to conventional chemotherapy and poor prognosis. However, the mechanisms involved in maintaining cancer stemness in CRC are still obscure and few clinical drugs were used to target cancer stemness. Previous studies had reported CD95 increases the stemness of cancer cells with long-term stimulation of exogenous agonist CD95 ligand (CD95L). However, the expression of CD95L is relative low in certain human tumor tissues. In this study, we found that CD95 was highly expressed in CRC cells, and in vitro it promoted the tumorsphere formation, chemotherapy resistance and in vivo tumor growth without stimulation of exogenous CD95L. Mechanistically, the bulk and single-cell RNA-sequencing results suggested that CD95 promotes stemness of CRC cells through upregulation of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1). MALAT1 knockdown inhibited CD95-induced tumorsphere formation and chemotherapy resistance. In summary, our findings reveal that CD95 has the capability to modulate cancer stemness via the action of the lncRNA MALAT1. Targeting CD95 may be a promising strategy to inhibit cancer stemness in CRC.

LncRNA Malat1 regulates iPSC-derived ß-cell differentiation by targeting the miR-15b-5p/Ihh axis.

BACKGROUND: Differentiation of induced pluripotent stem cells (iPSCs)-derived ß-like cells is a novel strategy for treatment of type 1 diabetes. Elucidation of the regulatory mechanisms of long noncoding RNAs (lncRNAs) in ß-like cells derived from iPSCs is important for understanding the development of the pancreas and pancreatic ß-cells and may improve the quality of ß-like cells for stem cell therapy. METHODS: ß-like cells were derived from iPSCs in a three-step protocol. RNA sequencing and bioinformatics analysis were carried out to screen the differentially expressed lncRNAs and identify the putative target genes separately. LncRNA Malat1 was chosen for further research. Series of loss and gain of functions experiments were performed to study the biological function of LncRNA Malat1. Quantitative real-time PCR (qRT-PCR), Western blot (WB) analysis and immunofluorescence (IF) staining were carried out to separately detect the functions of pancreatic ß-cells at the mRNA and protein levels. Cytoplasmic and nuclear RNA fractionation and fluorescence in situ hybridization (FISH) were used to determine the subcellar location of lncRNA Malat1 in ß-like cells. Enzyme-linked immunosorbent assays (ELISAs) were performed to examine the differentiation and insulin secretion of ß-like cells after stimulation with different glucose concentrations. Structural interactions between lncRNA Malat1 and miR-15b-5p and between miR-15b-5p/Ihh were detected by dual luciferase reporter assays (LRAs). RESULTS: We found that the expression of lncRNA Malat1 declined during differentiation, and overexpression (OE) of lncRNA Malat1 notably impaired the differentiation and maturation of ß-like cells derived from iPSCs in vitro and in vivo. Most importantly, lncRNA Malat1 could function as a competing endogenous RNA (ceRNA) of miR-15b-5p to regulate the expression of Ihh according to bioinformatics prediction, mechanistic analysis and downstream experiments. CONCLUSION: This study established an unreported regulatory network of lncRNA Malat1 and the miR-15b-5p/Ihh axis during the differentiation of iPSCs into ß-like cells. In addition to acting as an oncogene promoting tumorigenesis, lncRNA Malat1 may be an effective and novel target for treatment of diabetes in the future.

Micro electrical fields induced MSC-sEVs attenuate neuronal cell apoptosis by activating autophagy via lncRNA MALAT1/miR-22-3p/SIRT1/AMPK axis in spinal cord injury.

Spinal cord injury (SCI) is a traumatic condition of the central nervous system that causes paralysis of the limbs. Micro electric fields (EF) have been implicated in a novel therapeutic approach for nerve injury repair and regeneration, but the effects of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles that are induced by micro electric fields (EF-sEVs) stimulation on SCI remain unknown. The aim of the present study was to investigate whether EF-sEVs have therapeutic effects a rat model of SCI. EF-sEVs and normally conditioned human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (CON-sEVs) were collected and injected intralesionally into SCI model rats to evaluate the therapeutic effects. We detect the expression of candidate long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA-MALAT1) in EF-sEVs and CON-sEVs. The targets and downstream effectors of lncRNA-MALAT1 were investigated using luciferase reporter assays. Using both in vivo and in vitro experiments, we demonstrated that EF-sEVs increased autophagy and decreased apoptosis after SCI, which promoted the recovery of motor function. We further confirmed that the neuroprotective effects of EF-sEVs in vitro and in vivo correlated with the presence of encapsulated lncRNA-MALAT1 in sEVs. lncRNA-MALAT1 targeted miR-22-3p via sponging, reducing miR-22-3p's suppressive effects on its target, SIRT1, and this translated into AMPK phosphorylation and increased levels of the antiapoptotic protein Bcl-2. Collectively, the present study identified that the lncRNA-MALAT1 in EF-sEVs plays a neuroprotective role via the miRNA-22-3p/SIRT1/AMPK axis and offers a fresh perspective and a potential therapeutic approach using sEVs to improve SCI.

Roles of lncRNA-MALAT1 in the Progression and Prognosis of Gliomas.

Long noncoding RNAs (lncRNAs) represent a large subgroup of RNA transcripts that lack the function of coding proteins and may be essential universal genes involved in carcinogenesis and metastasis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNAMALAT1) is overexpressed in various human tumors, including gliomas. However, the biological function and molecular mechanism of action of lncRNA-MALAT1 in gliomas have not yet been systematically elucidated. Accumulating evidence suggests that the abnormal expression of lncRNA-MALAT1 in gliomas is associated with various physical properties of the glioma, such as tumor growth, metastasis, apoptosis, drug resistance, and prognosis. Furthermore, lncRNAs, as tumor progression and prognostic markers in gliomas, may affect tumorigenesis, proliferation of glioma stem cells, and drug resistance. In this review, we summarize the knowledge on the biological functions and prognostic value of lncRNA-MALAT1 in gliomas. This mini-review aims to deepen the understanding of lncRNA-MALAT1 as a novel potential therapeutic target for the individualized precision treatment of gliomas.

LncRNA MALAT1 Promoted Neuronal Necroptosis in Cerebral Ischemia-reperfusion Mice by Stabilizing HSP90.

The objective of this research was to investigate the role of lncRNA MALAT1 and HSP90 in the regulation of neuronal necroptosis in mice with cerebral ischemia-reperfusion (CIR). We used male C57BL/6J mice to establish a middle cerebral artery occlusion (MCAO) model and conducted in vitro experiments using the HT-22 mouse hippocampal neuron cell line. The cellular localization of NeuN and MLKL, as well as the expression levels of neuronal necroptosis factors, MALAT1, and HSP90 were analyzed. Cell viability and necroptosis were assessed, and we also investigated the relationship between MALAT1 and HSP90. The results showed that MALAT1 expression increased after MCAO and oxygen-glucose deprivation/re-oxygenation (OGD/R) treatment in both cerebral tissues and cells compared with the control group. The levels of neuronal necroptosis factors and the co-localization of NeuN and MLKL were also increased in MCAO mice compared with the Sham group. MALAT1 was found to interact with HSP90, and inhibition of HSP90 expression led to decreased phosphorylation levels of neuronal necroptosis factors. Inhibition of MALAT1 expression resulted in decreased co-localization levels of NeuN and MLKL, decreased phosphorylation levels of neuronal necroptosis factors, and reduced necroptosis rate in cerebral tissues. Furthermore, inhibiting MALAT1 expression also led to a shorter half-life of HSP90, increased ubiquitination level, and decreased phosphorylation levels of neuronal necroptosis factors in cells. In conclusion, this study demonstrated that lncRNA MALAT1 promotes neuronal necroptosis in CIR mice by stabilizing HSP90.

Predictive value of serum lncRNA MALAT1 for the recurrence of persistent atrial fibrillation after radiofrequency ablation.

Objective: The authors investigated the predictive value of MALAT1 for persistent atrial fibrillation (PAF) recurrence after radiofrequency ablation. Methods: Serum MALAT1 level was determined. The correlation between MALAT1 and high-sensitivity C-reactive protein/left atrial diameter (LAD) was analyzed. The predictive value of MALAT1 was evaluated. The postoperative recurrence rate in patients with high/low MALAT1 was compared. Independent risk factors for postoperative recurrence were analyzed. Results: MALAT1 was elevated in PAF patients and positively correlated with high-sensitivity C-reactive protein/LAD. MALAT1/high-sensitivity C-reactive protein/LAD were enhanced in patients with recurrent PAF. Patients with high MALAT1 had a higher recurrence rate. Upregulated MALAT1 was an independent risk factor for postoperative PAF recurrence. Conclusion: Serum MALAT1 level >2.03 predicts postoperative recurrence of PAF, and PAF patients with high MALAT1 have a higher risk of postoperative recurrence.

Atrial fibrillation (AF) is a common cardiac arrhythmia (abnormal heartbeat), which usually manifests as an irregular and rapid rhythm. In severe cases, AF can lead to cardiovascular diseases such as thromboembolism (narrowing and blockage of blood vessels) and heart failure (impaired pumping function of the heart). Cardiac radiofrequency ablation is a common method used to treat AF. However, patients with PAF still have a high rate of late recurrence after the operation, so there is an urgent need to identify suitable biochemical markers for predicting the postoperative recurrence of PAF. lncRNAs are a type of noncoding nucleic acid; they do not encode proteins, have various biological functions and are widely distributed in living organisms. The lncRNA MALAT1 has been considered a potential therapeutic target and biomarker in several cardiovascular diseases. This study demonstrated that the serum level of MALAT1 in PAF patients was significantly higher than that in normal subjects and MALAT1 level was elevated in patients with recurrent PAF compared with patients without recurrence. The authors also found that serum MALAT1 could predict whether PAF will recur after operation, with a high accuracy. In addition, PAF patients with high expression of serum MALAT1 had a higher risk of postoperative recurrence. In summary, serum level of lncRNA MALAT1 can help predict postoperative recurrence of PAF and a high level of MALAT1 is indicative of a higher risk of postoperative recurrence. Analysis of serum lncRNA MALAT1 level in PAF patients before surgery can predict postoperative recurrence, and intervention programs that lower the MALAT1 level can be implemented to reduce the risk of postoperative recurrence of PAF and increase the success rate of the operation. This study has important implications for reducing the recurrence rate after radiofrequency ablation in PAF patients.

Association of long noncoding RNA MALAT1 with the radiosensitivity of lung adenocarcinoma cells via the miR-140/PD-L1 axis.

Objective: To investigate the effect of MALAT1 on the modulating the radiosensitivity of lung adenocarcinoma, through regulation of the expression of the miR-140/PD-L1 axis. Methods: The online databases UALCAN and dbDEMC were searched for the MALAT1 and miR-140 expressions in patients with lung adenocarcinoma (LUAD), respectively. Then analyze their relationship with overall survival rates separately in the UALCAN and ONCOMIR databases. A functional analysis was performed for A549 cells by transfecting small-interfering RNAs or corresponding plasmids after radiotherapy. Xenograft models of LUAD exposed to radiation were established to further observe the effects of MALAT1 on the radiosensitivity of LUAD. The luciferase assay and reverse transcription-polymerase chain reaction were performed to assess the interaction between miR-140 and MALAT1 or PD-L1. Results: MALAT1 were overexpressed in human LUAD tumor tissues and cell lines, while miR-140 were inhibited. MALAT1 knockdown or miR-140 increase suppressed cell proliferation and promoted cell apoptosis in LUAD after irradiation. LUAD xenograft tumor growth was also inhibited by MALAT1 knockdown combined with irradiation. miR-140 could directly bind with MALAT1 or PD-L1. Furthermore, MALAT1 knockdown inhibited PD-L1 mRNA and protein expressions by upregulating miR-140 in LUAD cells. Conclusion: MALAT1 may function as a sponge for miR-140a-3p to enhance the PD-L1 expression and decrease the radiosensitivity of LUAD. Our results suggest that MALAT1 might be a promising therapeutic target for the radiotherapy sensitization of LUAD.

LncRNA MALAT 1/miR-625-3p/HIF-1α axis regulates the EMT of hypoxia-induced RPE cells by activating NF-κB/snail signaling.

The retina may undergo structural and functional damage as a result of hypoxia, which could lead to permanent blindness. As competing endogenous RNAs (ceRNAs), lncRNAs are essential in eye disorders. The biological function of lncRNA MALAT 1 and its potential mechanisms in hypoxic-ischemic retinal diseases are still unknown. MALAT 1 and miR-625-3p expression alterations in hypoxia-treated RPE cells were examined using qRT-PCR. The target binding relationships between MALAT 1 and miR-625-3p, as well as between miR-625-3p and HIF-1α, were identified utilizing bioinformatics analysis and dual luciferase reporter assay. We observed that si-MALAT 1 and miR-625-3p mimic both reduced apoptosis and epithelial-mesenchymal transition (EMT) in hypoxic RPE cells, whereas si-MALAT 1 was reversed by miR-625-3p inhibitor. Further, we carried out a mechanistic investigation, and rescue assays demonstrated that MALAT 1 sponging miR-625-3p influenced HIF-1α expression and consequently took part in the NF-κB/Snail signaling pathway, which regulated apoptosis and EMT. In conclusion, our research had shown that the MALAT 1/miR-625-3p/HIF-1α axis drove the progression of hypoxic-ischemic retinal disorders and may serve as a promising predictive biomarker for their therapeutic and diagnostic targets.

LncRNA-MALAT1: A Key Participant in the Occurrence and Development of Cancer.

LncRNAs are a group of non-coding RNA transcripts with lengths of over 200 nucleotides and can interact with DNA, RNA, and proteins to regulate gene expression of malignant tumors in human tissues. LncRNAs participate in vital processes, such as chromosomal nuclear transport in the cancerous site of human tissue, activation, and the regulation of proto-oncogenes, the differentiation of immune cells, and the regulation of the cellular immune system. The lncRNA metastasis-associated lung cancer transcript 1 (MALAT1) is reportedly involved in the occurrence and development of many cancers and serves as a biomarker and therapeutic target. These findings highlight its promising role in cancer treatment. In this article, we comprehensively summarized the structure and functions of lncRNA, notably the discoveries of lncRNA-MALAT1 in different cancers, the action mechanisms, and the ongoing research on new drug development. We believe our review would serve as a basis for further research on the pathological mechanism of lncRNA-MALAT1 in cancer and provide evidence and novel insights into its application in clinical diagnoses and treatments.

Knockdown of the long non­coding RNA MALAT1 ameliorates TNF­α­mediated endothelial cell pyroptosis via the miR­30c­5p/Cx43 axis.

Long noncoding RNAs (lncRNAs) are related to the development of atherosclerosis (AS). However, the role of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in tumor necrosis factor­α (TNF­α)­induced rat aortic endothelial cell (RAOEC) pyroptosis, as well as the underlying mechanisms, remain unclear. RAOEC morphology was assessed using an inverted microscope. The mRNA and/or protein expression levels of MALAT1, microRNA(miR)­30c­5p and connexin 43 (Cx43) were assessed using reverse transcription­quantitative PCR (RT­qPCR) and/or western blotting, respectively. The relationships among these molecules were validated by dual­luciferase reporter assays. Biological functions, such as LDH release, pyroptosis­associated protein levels and the proportion of PI­positive cells, were evaluated using a LDH assay kit, western blotting and Hoechst 33342/PI staining, respectively. The present study demonstrated that compared with the control group, the mRNA expression levels of MALAT1 and protein expression levels of Cx43 were significantly up­regulated, whereas miR­30c­5p mRNA expressions levels were significantly decreased in TNF­α­treated RAOEC pyroptosis. Knockdown of MALAT1 or Cx43 significantly attenuated the increase in LDH release, pyroptosis­associated protein expression and PI­positive cell numbers among RAOEC treated using TNF­α, whereas an miR­30c­5p mimic exerted the opposite effect. Furthermore, miR­30c­5p was demonstrated to be a negative regulator of MALAT1 and could also target Cx43. Finally, co­transfection with siMALAT1 and miR­30c­5p inhibitor could attenuate the protective effect of MALAT1 knockdown against TNF­α­mediated RAOEC pyroptosis by upregulation of Cx43 expression. In conclusion, MALAT1 might serve an important role in TNF­α­mediated RAOEC pyroptosis by regulating the miR­30c­5p/Cx43 axis, which would provide a potential novel diagnostic and therapeutic target for AS.