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Purpose: Epithelial–mesenchymal transition (EMT) is a crucial pathological process that contributes to proliferative vitreoretinopathy (PVR), and research indicates that factors present in the vitreous that target cells play pivotal roles in regulating EMT. Experimental studies have confirmed that rabbit vitreous (RV) promotes EMT in human retinal pigment epithelial (RPE) cells. The long noncoding RNA (lncRNA) MALAT1 has been implicated in EMT in various diseases. Thus, this study aimed to investigate the involvement of lncRNA MALAT1 in vitreous-induced EMT in RPE cells. Methods: MALAT1 was knocked down in ARPE-19 cells by short hairpin RNA (shRNA) transfection. Reverse transcription PCR (RT‒PCR) was used to evaluate MALAT1 expression, and Western blotting analysis was used to measure the expression of EMT-related proteins. Wound-healing, Transwell, and cell contraction assays were conducted to assess cell migration, invasion, and contraction, respectively. Additionally, cell proliferation was assessed using the CCK-8 assay, and cytoskeletal changes were examined by immunofluorescence. Results: MALAT1 expression was significantly increased in ARPE-19 cells cultured with RV. Silencing MALAT1 effectively suppressed EMT and downregulated the associated factors snail1 and E-cadherin. Furthermore, silencing MALAT1 inhibited the RV-induced migration, invasion, proliferation, and contraction of ARPE-19 cells. Silencing MALAT1 also decreased RV-induced AKT and P53 phosphorylation. Conclusions: In conclusion, lncRNA MALAT1 participates in regulating vitreous-induced EMT in human RPE cells; these results provide new insight into the pathogenesis of PVR and offer a potential direction for the development of antiproliferative drugs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) belongs to the long non-coding RNA (LncRNA) family. LncRNA-MALAT1 is expressed in a variety of tissues and is involved in a variety of diseases and biological processes. Although LncRNA-MALAT1 is upregulated in a high-glucose microenvironment and may participate in odontogenic differentiation, the underlying mechanism is not yet well elucidated. Here, we show that MALAT1 was mainly expressed in the cytoplasm of dental pulp cells (DPCs) in situ hybridization. In addition, high levels of mineralization-related factors, namely, tumor growth factors β 1 and 2 (TGFβ-1 and TGFβ-2), bone morphogenetic proteins 2 and 4 (BMP2 and BMP4), bone morphogenetic protein receptor 1 (BMPR1), SMAD family member 2 (SMAD2), runt-related transcription factor 2 (RUNX2), Msh homeobox 2 (MSX2), transcription factor SP7 (SP7), alkaline phosphatase (ALP), dentin matrix acidic phosphoprotein 1 (DMP1), and dentin sialophosphoprotein (DSPP), were expressed, and MALAT1 was significantly overexpressed in DPCs 7 and 14 days after mineralization induction in a high-glucose microenvironment, but only TGFβ-1, BMP2, MSX2, SP7, ALP, and DSPP were significantly downregulated in DPCs after MALAT1 inhibition. MALAT1 may participate in the mineralization process of DPCs by regulating multiple factors (TGFβ-1, BMP2, MSX2, SP7, ALP, and DSPP).

Objective: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play key roles in cancer. This study aims to clarify role of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in non-small cell lung cancer (NSCLC) and uncover the underlying mechanisms. Materials and Methods: In this experimental study, MALAT1 and miR-202 expression in tissues and cell lines were detected using quantitative real time polymerase chain reaction (qRT-PCR) assay. Cell transfection was conducted using Lipofectamine 3000. Cell proliferation was determined with CCK-8 assay. MMP2 and MMP9 expressions were measured with Western blot. Cell invasive ability was evaluated by Transwell assay. Starbase 2.0 tool was used to predict targets of MALAT1. Dual luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA pull-down assay were conducted to confirm the potential direct interaction between MALAT1 and miR-202. Results: MALAT1 was overexpressed in NSCLC samples and cell lines. High expression of MALAT1 was related to large tumor size (>3 cm), poor histological grade, advanced cancer and tumor metastasis in NSCLC. In vitro assays exhibited that knockdown of MALAT1 remarkably decreased A549 cell growth and invasion capacity, while overexpression of MALAT1 significantly enhanced NCI-H292 cell proliferation and invasion ability. Next, we verified that MALAT1 could act as a competing endogenous RNA (ceRNA) by sponging miR-202 in NSCLC and there is a negative correlation between MALAT1 and miR-202. Besides, overexpression of miR-202 inhibited cell proliferation and invasive ability in MALAT1-overexpressed cells. Conclusion: This study demonstrated that lncRNA-MALAT1 gets involved in NSCLC progression by targeting miR- 202, indicating that MALAT1 may serve as a novel therapeutic target for NSCLC treatment.

Environmental, genetic and epigenetic risk factors have been closely related to the development of type-2 diabetes (T2D). It has been reported that the expression in H19 and MALAT1 are related to metabolic diseases. To analyze the relationship between the expression of H19 and MALAT1 lncRNAs with diabetic patients. A study was conducted in subjects with T2D and nondiabetic controls, residents of Mexico City. Anthropometric measurements were made, and serum concentrations of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol were analyzed. Total RNA was extracted from serum and serum exosomes. The H19 and MALAT1 expression levels were quantified by RT-qPCR. A significant reduction in the expression of MALAT1 from serum or serum exosomes were found in patients with T2D, metabolic syndrome and low levels of HDL-c. Significant increase in H19 levels was found in diabetic subjects with poor glycemic control. Additionally, the principal component analyzes showed that serum MALAT1 expression was associated with total cholesterol and HDL-c levels, and the exosomes H19 expression was associated with waist circumference. The results obtained suggest that MALAT1 expression levels could be an epigenetic biomarker of diabetes risk or of its comorbidities.

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.

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.

OBJECTIVE: Long non-coding ribonucleic acid-metastasis-associated lung adenocarcinoma transcript 1 (lncRNA-MALAT1) has been confirmed as a key factor involving in various physiological and pathological processes. The present study aims to investigate whether lncRNA-MALAT1 affects the process of myocardial infarction (MI) in rats by regulating the micro RNA (miR-30a)/Beclin-1 (BECN1) pathway. MATERIALS AND METHODS: Twelve healthy male Sprague-Dawley rats were randomly selected and equally divided into sham-operation group and MI group. In MI group, a rat model of acute MI (AMI) was established by ligating the left anterior descending coronary artery. Rats in sham-operation group were set as the control. The messenger RNA (mRNA) expression levels of lncRNA-MALAT1, miR-30a, and BECN1 in the infarcted myocardial tissues were detected via real-time fluorescence quantitative polymerase chain reaction (qRTPCR). The rat myocardial cell line H9c2 was cultured in vitro and then transfected with vectors of lncRNA-MALAT1, miR-30a, and BECN1. After that, qRT-PCR was performed to measure mRNA levels of lncRNA-MALAT1, miR-30a, and BECN1 in H9c2 cells. The protein level of BECN1 in cells was determined via Western blotting (WB) assay. RESULTS: Expression levels of lncRNA-MALAT1 and BECN1 in the rat myocardium of MI group were up-regulated markedly (p<0.01), while miR-30a was down-regulated notably (p<0.01) compared with those in sham-operation group. After H9c2 cells were transfected with overexpression vectors of lncRNA-MALAT1 or miR-30a, expression levels of miR-30a (p<0.01) and BECN1 (p<0.01) were remarkably down-regulated, respectively. CONCLUSIONS: LncRNA-MALAT1 up-regulates the expression of BECN1 by binding to miR-30a, thereby increasing the level of cell autophagy after MI. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the regulatory effect of long non-coding ribonucleic acid (lncRNA)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway, and to explore its influence on neuronal apoptosis in rats with cerebral infarction. MATERIALS AND METHODS: A total of 45 adult male Sprague-Dawley rats were randomly divided into sham group (n=15), model group (n=15) and MALAT1 low-expression group (n=15). The model of cerebral infarction was successfully established in the model group and MALAT1 low-expression group via middle cerebral artery occlusion (MCAO). After 3 d, the nerve injury in each group was evaluated using Zea-Longa score. Meanwhile, the area of cerebral infarction in each group was detected via 2,3,5-triphenyl tetrazolium chloride (TTC) staining. After the cortical tissues were separated, the expression level of lncRNA-MALAT1 was detected via quantitative Polymerase Chain Reaction (qPCR). The apoptotic level of neurons in each group was detected via terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) staining. The expression levels of inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, the expression levels of apoptosis-related proteins and ERK/MAPK signaling pathway-related proteins were detected via Western blotting. RESULTS: Compared with the sham group, the behavioral score and area of cerebral infarction in the model group were significantly increased (p<0.01). The low expression of MALAT1 could effectively reduce the behavioral score and area of cerebral infarction in the model group (p<0.01). The expression level of lncRNA-MALAT1 in cortical tissues of the model group was markedly higher than that of the sham group and MALAT1 low-expression group (p<0.01). Compared with the sham group, the content of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cortical tissues was significantly increased (p<0.01). However, the content of IL-10 was remarkably decreased in the model group (p<0.01). Low expressed MALAT1 could markedly reduce the content of TNF-α and IL-6 and increase the content of IL-10 in cortical tissues (p<0.01). The level of apoptosis in cortical tissues was increased in the model group when compared with that of the sham group (p<0.01). Meanwhile, low expression of MALAT1 could effectively reduce the apoptosis level in cortical tissues in model group (p<0.01). In the model group, the expression levels of B-cell lymphoma-2/Bcl-2 associated X protein (Bcl-2/Bax), p-ERK and matrix metalloproteinase-2 (MMP-2) in cortical tissues were significantly declined than the sham group (p<0.01). However, the protein expression level of cleaved caspase-3 was markedly increased (p<0.01). Furthermore, the low expression of MALAT1 could remarkably increase the expressions of Bcl-2/Bax, p-ERK and MMP-2 (p<0.01), as well as decrease the expression of cleaved caspase-3 (p<0.01). CONCLUSIONS: LncRNA-MALAT1 may increase the release of inflammatory cytokines by inhibiting the ERK/MAPK signaling pathway, thereby up-regulating the level of neuronal apoptosis and aggravating the cerebral injury in rats with cerebral infarction. [ABSTRACT FROM AUTHOR]

Bone repair involves bone resorption through osteoclastogenesis and the stimulation of neovascularization and osteogenesis by endothelial progenitor cells (EPCs). However, the role of EPCs in osteoclastogenesis is unclear. In this study, we assess the effects of EPC‐derived exosomes on the migration and osteoclastic differentiation of primary mouse bone marrow‐derived macrophages (BMMs) in vitro using immunofluorescence, western blotting, RT‐PCR and Transwell assays. We also evaluated the effects of EPC‐derived exosomes on the homing and osteoclastic differentiation of transplanted BMMs in a mouse bone fracture model in vivo. We found that EPCs cultured with BMMs secreted exosomes into the medium and, compared with EPCs, exosomes had a higher expression level of LncRNA‐MALAT1. We confirmed that LncRNA‐MALAT1 directly binds to miR‐124 to negatively control miR‐124 activity. Moreover, overexpression of miR‐124 could reverse the migration and osteoclastic differentiation of BMMs induced by EPC‐derived exosomes. A dual‐luciferase reporter assay indicated that the integrin ITGB1 is the target of miR‐124. Mice treated with EPC‐derived exosome‐BMM co‐transplantations exhibited increased neovascularization at the fracture site and enhanced fracture healing compared with those treated with BMMs alone. Overall, our results suggest that EPC‐derived exosomes can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors through LncRNA‐MALAT1. [ABSTRACT FROM AUTHOR]

Endometriosis is a common gynecological disease characterized by diminished apoptosis, sustained ectopic survival of dysfunctional endometrial cells. Hypoxia has been implicated as a crucial microenvironmental factor that contributes to endometriosis. It has been reported that long non‐coding RNA MALAT1 (lncRNA‐MALAT1) highly expressed in endometriosis and up‐regulated by hypoxia. Hypoxia may also induce autophagy, which might act as cell protective mechanism. However, the relationship between lncRNA‐MALAT1 and autophagy under hypoxia conditions in endometriosis remains unknown. In the present study, we found that both lncRNA‐MALAT1 and autophagy level were up‐regulated in ectopic endometrium from patients with endometriosis, and its expression level correlates positively with that of hypoxia‐inducible factor‐1α (HIF‐1α). In cultured human endometrial stromal cells, both lncRNA‐MALAT1 and autophagy were induced by hypoxia in a time‐dependent manner and lncRNA‐MALAT1 up‐regulation was dependent on HIF‐1α signalling. Our analyses also show that knockdown of lncRNA‐MALAT1 suppressed hypoxia induced autophagy. Furthermore, inhibiting autophagy with specific inhibitor 3‐Methyladenine (3‐MA) and Beclin1 siRNA enhanced apoptosis of human endometrial stromal cells under hypoxia condition. Collectively, our findings identify that lncRNA‐MALAT1 mediates hypoxia‐induced pro‐survival autophagy of endometrial stromal cells in endometriosis. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is a chronic inflammatory disease. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs have emerged as critical regulators of atherosclerosis; however, whether they have crosstalk on this issue remains elusive. Here, we investigated the potential associations between lncRNA-MALAT1 and miR-155 on the regulation of atherosclerosis.Methods: Quantitative real-time PCR was employed to assess the expression of MALAT1, IL-6 and IL-8. ELISA was performed to measure the secretion of IL-6 and IL-8. MTT assay was used to determine the proliferation of Human Coronary Artery Endothelial Cells (HCAECs). Flow cytometry was used to measure the cell apoptosis. Western blot was used to assess the expression of apoptosis-related proteins and the phosphorylation of STAT1 and STAT3.Results: We found that the pro-inflammatory cytokine release and the apoptosis of HCAECs were elevated upon ox-LDL treatment, while MALAT1 expression was also up regulated. Knocking down of MALAT1 boosted ox-LDL-induced cytokine release and apoptosis of HCAECs. The binding site of miR-155 in MALAT1 sequence was confirmed by dual luciferase assay. Furthermore, miR-155 inhibition significantly repressed ox-LDL mediated inflammation and apoptosis of HCAECs via SOCS1. At last, we found that MALAT1 could suppress the inflammatory cytokine release and cell apoptosis via sponging miR-155 to increase SOCS1 level, which in turn restrained JAK-STAT pathway.Conclusion: In summary, this study revealed the mechanisms by which MALAT1 worked as a putative atherosclerosis suppressor via miR-155 and SOCS1. Therefore, modulation of MALAT1/miR-155/SOCS1 axis might alleviate the inflammation persisted in atherosclerosis. [ABSTRACT FROM AUTHOR]

Recently, emerging evidence has demonstrated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNAs (lncRNAs), contributes to the initiation and development of tumors, including osteosarcoma (OS). Multiple studies have suggested an oncogenic role of MALAT1 and high-mobility group protein B1 (HMGB1) in OS tumorigenesis and metastasis, but the effects and mechanisms are not unanimous. Here, we showed that MALAT1 and HMGB1 were significantly increased in human OS cell lines and knockdown of MALAT1 reduced HMGB1 expression. By using online tools, we screen out 2 candidate miRNAs, miR-142–3p and miR-129–5p which may be associated with both MALAT1 and HMGB1. Luciferase reporter assay revealed a direct interaction between the 2 miRNAs and MALAT1, respectively, via a putative binding site within MALAT1. Meanwhile, both the 2 miRNAs could bind to HMGB1 3′-untranslated region (3′-UTR) and regulate HMGB1 expression. Moreover, knockdown of MALAT1 decreased HMGB1 expression, inhibited OS cell growth and promoted apoptosis, while miR-142–3p and miR-129–5p inhibitor partly restored the inhibitory effect of MALAT1 knockdown on HMGB1 expression, OS cell growth and the promotion of apoptosis. In OS tissues, the expression of MALAT1 and HMGB1 was upregulated while the expression of miR-142–3p and miR-129–5p was downregulated. Together, our results support a MALAT1/miR-142–3p/miR-129–5p/HMGB1 axis in OS cell proliferation and tumor progression. MALAT1 promoted OS cell growth through inhibition of miR-142–3p or miR-129–5p and by targeting HMGB1. [ABSTRACT FROM PUBLISHER]

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) belongs to the long non-coding RNA (LncRNA) family. LncRNA-MALAT1 is expressed in a variety of tissues and is involved in a variety of diseases and biological processes. Although LncRNA-MALAT1 is upregulated in a high-glucose microenvironment and may participate in odontogenic differentiation, the underlying mechanism is not yet well elucidated. Here, we show that MALAT1 was mainly expressed in the cytoplasm of dental pulp cells (DPCs) in situ hybridization. In addition, high levels of mineralization-related factors, namely, tumor growth factors β 1 and 2 (TGFβ-1 and TGFβ-2), bone morphogenetic proteins 2 and 4 (BMP2 and BMP4), bone morphogenetic protein receptor 1 (BMPR1), SMAD family member 2 (SMAD2), runt-related transcription factor 2 (RUNX2), Msh homeobox 2 (MSX2), transcription factor SP7 (SP7), alkaline phosphatase (ALP), dentin matrix acidic phosphoprotein 1 (DMP1), and dentin sialophosphoprotein (DSPP), were expressed, and MALAT1 was significantly overexpressed in DPCs 7 and 14 days after mineralization induction in a high-glucose microenvironment, but only TGFβ-1, BMP2, MSX2, SP7, ALP, and DSPP were significantly downregulated in DPCs after MALAT1 inhibition. MALAT1 may participate in the mineralization process of DPCs by regulating multiple factors (TGFβ-1, BMP2, MSX2, SP7, ALP, and DSPP)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Xu, Lin, Wu and Wu.)

Deep vein thrombosis (DVT) is a vascular disease. The long non-coding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), is positively expressed in DVT tissues, and regulates the biological behavior of endothelial progenitor cells. Here, we explored whether MALAT1 affected the physiology of human vascular endothelial cells (HUVECs) and analyzed its underlying mechanism. To overexpress/silence the expression of MALAT1 in HUVECs, MALAT1-plasmid/MALAT1-small interfering RNA (siRNA) was used. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and flow cytometry analyses were performed to observe the cell viability and apoptosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to determine the apoptosis-related protein and gene expression levels. We used Starbase software to predict the associations among MALAT1, microRNA (miR)-383-5p, and BCL2-like 11 (BCL2L11). Luciferase reporter assay was used to validate their relationship. Compared to the control vector group, MALAT1-plasmid suppressed the viability and induced apoptosis of HUVECs, while improving Bcl-2-associated X protein (Bax) expression and decreasing Bcl-2 expression. There was an interaction between MALAT1 and miR-383-5p. Compared to the control siRNA group, MALAT1-siRNA increased the cell viability, reduced cell apoptosis, upregulated Bcl-2 expression, and suppressed Bax expression. These changes were reversed by the miR-383-5p inhibitor. Additionally, we verified that BCL2L11 is a target of miR-383-5p. miR-383-5p improved the cell proliferation, while decreasing cell apoptosis in HUVECs by targeting BCL2L11. Therefore, the lncRNA-MALAT1/miR-383-5p/BCL2L11 axis may be effective for DVT treatment.

[Display omitted] Based on the previous studies, this study was carried out to explore the interaction of LncRNA-Malat1/miR-211-5p in cerebral ischemia reperfusion injury (CIRI). Firstly, the expression changes of LncRNA-MALAT1 and miR-211-5p in ischemia patients' blood were determined, and the binding sites of them were predicted by bioinformatics. Furthermore, middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established in adult male SD rats, and primary neuronal oxygen-glucose deprivation/reoxygen-glucose reoxygenation (OGD/R) was established in vitro. The results showed that LncRNA-MALAT1 was significantly up-regulated and miR-211-5p down-regulated in the peripheral blood of patients with ischemic stroke, and the expression changes were negatively correlated. Bioinformatics prediction results showed that LncRNA-MALAT1 had a binding site with miR-211-5p. We also found that LncRNA-Malat1 was significantly up-regulated while miR-211-5p down-regulated in rat cortex tissue and primary neurons treated with OGD/R. In addition, lentivirus interfered with LV-Malat1-RNAi decreased the expression of LncRNA-Malat1 and promoted the up-regulation of miR-211-5p. Combination of LV-Malat1-RNAi and miR-211-5p inhibitor significantly reversed the protective effect of down-regulation of LncRNA-Malat1. Inhibition of LncRNA-Malat1 expression alleviated the neurological deficit score after MCAO/R, improved histopathological damage, and reduced the size of cerebral infarction. Combined administration of LV-Malat1-RNAi + Antagomir-211-5p reversed these effects above. In short, our data suggest that LncRNA-Malat is involved in the occurrence and development of cerebral ischemia reperfusion injury by acting on miR-211-5p and is then regulating the expression of COX-2. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of deadly malignancies that affects humans globally. Herein, the effects of MALAT1 on CRC cellular functions were investigated. RT-qPCR measured expression of MALAT1 in human cell lines for colorectal Cancer. Radiation-resistance CRC cells (CRC-IR) were generated by increasing treatments of irradiation. Cell transfection upregulated or silenced genes in CRC-IR cells so as to study the correlation between MALAT1/miR-101-3p expression and cellular resistance to irradiation through evaluation of CCK-8, FCM apoptosis, Transwell migration and invasion and western blot assays for cell viability,apoptosis, migration and invasion and EMT. MALAT1 was upregulated in radio-resistance cell lines compared to normal CRC cells and upregulation promoted cell viability. In addition, decreased MALAT1 inhibited cell proliferation and metastasis and promoted apoptosis of CRC-IR cells. The luciferase assays confirmed that MALAT1 targeted and regulated miR-101-3p expression in radio-resistance cells. MiR-101-3p counteracted the effect exerted by MALAT1 in CRC-IR cells, indicating that MALAT1 added to the radio-resistance in vitro while miR-101-3p mimics could decrease the resistance to irradiation in CRC. In this study we have demonstrated that MALAT1 could regulate the radio-resistance in colorectal cancer via sponging miR-101-3p. Eventually, these outcomes unearthed a novel axis lncRNA MALAT1/miR-101-3p,which might be a prospective treatment to regulate radio-therapy in the near future. [ABSTRACT FROM AUTHOR]

Neonatal bronchopulmonary dysplasia (BPD) is one of the common causes of premature birth complications, which is caused by lung dysplasia. Long non-coding RNA (LncRNA) has been proved to be related to BPD and other disease processes, but the molecular mechanism of metastasis-related lung adenocarcinoma transcript 1 (MALAT1) in BPD has not been fully understood. This study focused on exploring the clinical and molecular mechanism of MALAT1 in neonatal BPD, aiming to provide new insights for the management of neonatal BPD. In our study, we first found that serum MALAT1 was up-regulated in neonatal BPD and severe BPD. Further, through receiver operating characteristic curve (ROC) analysis, it was found that the area under the curve of MALAT1 for differentiating neonatal BPD from severe BPD was 0.943 and 0.866, respectively. Then, we established BPD models in vivo and in vitro with C57BL/6J mice and BEAS-2B cells, and found that MALAT1 was also highly expressed in them and increased with the induction time of the models. Pathological evaluation confirmed that down-regulating MALAT1 or up-regulating miR-206 might improve the pathological condition of BPD. Obvious inflammatory response, oxidative stress and up-regulated apoptosis were observed in BPD models in vivo and in vitro. However, after MALAT1 knockdown treatment, the above abnormal phenomena were alleviated to varying degrees. Furthermore, we also found that MALAT1 has a targeted relationship with miR-206, and miR-206 is down-regulated in BPD in vivo and in vitro. Down-regulating miR-206 could also eliminate the anti-BPD effect after knocking down MALAT1. The above results indicated that MALAT1 has the potential as a blood biomarker of neonatal BPD, and MALAT1-miR-206 axis mediates BPD process, which may be a new target for neonatal BPD treatment., Competing Interests: None., (AJTR Copyright © 2021.)

Objective: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play key roles in cancer. This study aims to clarify role of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in non-small cell lung cancer (NSCLC) and uncover the underlying mechanisms., Materials and Methods: In this experimental study, MALAT1 and miR-202 expression in tissues and cell lines were detected using quantitative real time polymerase chain reaction (qRT-PCR) assay. Cell transfection was conducted using Lipofectamine 3000. Cell proliferation was determined with CCK-8 assay. MMP2 and MMP9 expressions were measured with Western blot. Cell invasive ability was evaluated by Transwell assay. Starbase 2.0 tool was used to predict targets of MALAT1 . Dual luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA pull-down assay were conducted to confirm the potential direct interaction between MALAT1 and miR-202 ., Results: MALAT1 was overexpressed in NSCLC samples and cell lines. High expression of MALAT1 was related to large tumor size (>3 cm), poor histological grade, advanced cancer and tumor metastasis in NSCLC. In vitro assays exhibited that knockdown of MALAT1 remarkably decreased A549 cell growth and invasion capacity, while overexpression of MALAT1 significantly enhanced NCI-H292 cell proliferation and invasion ability. Next, we verified that MALAT1 could act as a competing endogenous RNA (ceRNA) by sponging miR-202 in NSCLC and there is a negative correlation between MALAT1 and miR-202 . Besides, overexpression of miR-202 inhibited cell proliferation and invasive ability in MALAT1-overexpressed cells., Conclusion: This study demonstrated that lncRNA-MALAT1 gets involved in NSCLC progression by targeting miR-202 , indicating that MALAT1 may serve as a novel therapeutic target for NSCLC treatment., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

This study aimed to explore the expression of lncRNA-metastasis associated lung adenocarcinoma transcript 1 (lncRNA-MALAT1) in breast cancer (BC) patients and its influences on the prognosis of the patients. A total of 120 BC patients admitted to our hospital were enrolled as a BC group, of which 58 patients at I/II stage were treated with breast-conserving surgery as an operation group, and the other 62 patients at III/IV stage were treated with neoadjuvant chemotherapy combined with breast-conserving surgery as a combination group. Meantime, 100 healthy people in physical examination during the same period were enrolled as a normal group. The expression of serum lncRNA-MALAT1 in the subjects was determined, and the expression in BC patients and its influences on the patients were analyzed. LncRNA-MALAT1 was over-expressed in patients from the BC group, and the area-under-the-curve (AUC) of it for diagnosing BC was 0.911. After treatment, the expression of lncRNA-MALAT1 in the operation group and the combination group significantly decreased, and the expression of it in patients with good prognosis was greatly lower than that in patients with poor prognosis. The AUC of lncRNA-MALAT1 for predicting poor prognosis was 0.838, and TNM staging, pathological differentiation, tumor diameter, and lncRNA-MALAT1 were independent prognostic factors for poor prognosis of the patients. Furthermore, low expression of lncRNA-MALAT1 was associated with a relatively high 5-year overall survival (OS) of BC patients. The expression of lncRNA-MALAT1 was up-regulated in BC patients, while it was down-regulated in BC patients treated with breast-conserving surgery combined with neo-adjuvant chemotherapy, so lncRNA-MALAT1 can be used as a potential indicator for early diagnosis and prognosis prediction of BC patients.

Environmental, genetic and epigenetic risk factors have been closely related to the development of type-2 diabetes (T2D). It has been reported that the expression in H19 and MALAT1 are related to metabolic diseases. To analyze the relationship between the expression of H19 and MALAT1 lncRNAs with diabetic patients. A study was conducted in subjects with T2D and nondiabetic controls, residents of Mexico City. Anthropometric measurements were made, and serum concentrations of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol were analyzed. Total RNA was extracted from serum and serum exosomes. The H19 and MALAT1 expression levels were quantified by RT-qPCR. A significant reduction in the expression of MALAT1 from serum or serum exosomes were found in patients with T2D, metabolic syndrome and low levels of HDL-c. Significant increase in H19 levels was found in diabetic subjects with poor glycemic control. Additionally, the principal component analyzes showed that serum MALAT1 expression was associated with total cholesterol and HDL-c levels, and the exosomes H19 expression was associated with waist circumference. The results obtained suggest that MALAT1 expression levels could be an epigenetic biomarker of diabetes risk or of its comorbidities., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

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., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

This study aimed to explore the correlation of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) expression with acute respiratory distress syndrome (ARDS) risk, disease severity, inflammation level, and mortality in septic patients. 152 septic patients were consecutively included and surveillance was conducted daily to identify ARDS occurrence. Severity and organ failure of sepsis were assessed by APACHE II score and SOFA score respectively, and the in-hospital mortality was calculated. Patients' blood samples were extracted. Lnc-MALAT1 expression and inflammatory cytokines levels were detected using real-time qPCR and ELISA assay respectively. The incidence of ARDS was 27.0%. Lnc-MALAT1 expression was increased in ARDS patients compared to non-ARDS patients, and it could distinguish ARDS from non-ARDS by ROC with AUC of 0.674 (95% CI: 0.581-0.766). Multivariate logistic regression analysis displayed that lnc-MALAT1 high expression, increased age, higher proportion of smoking and COPD were independent factors for predicting elevated ARDS risk. Lnc-MALAT1 expression was positively correlated with APACHE II score, SOFA score, and inflammatory factors levels including C-reactive protein, procalcitonin, TNF-α, IL-1β, IL-6 and IL-17. Furthermore, the mortality was 30.9%, and lnc-MALAT1 expression was elevated in non-survivors compared to survivors, presenting a good predictive value for high mortality by ROC with AUC of 0.651 (95% CI: 0.555-0.747). Lnc-MALAT1 high expression predicts increased ARDS risk, and correlates with severe disease condition and raised mortality in sepsis patients., Competing Interests: None., (IJCEP Copyright © 2019.)

Stroke is one of the leading causes of death and long-term disability around the world. Angiogenesis is supposed to protect brain microvascular endothelial cells (BMECs) from oxidative and ischemic stress. Previous studies indicated that interaction between metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-145 was involved in myocardial ischemia reperfusion, suggesting MALAT1 and miR-145 were also mediated with the progress of angiogenesis and cell migration in oxygen-glucose deprivation (OGD)-induced BMECs. The present study aimed to investigate the functional roles of MALAT1 in regulating miR-145 and its downstream pro-angiogenesis factors, vascular endothelial growth factor (VEGF)-A and Angiopoietin-2 (ANGPT2) during the progress of angiogenesis in OGD-induced BMECs. An in vitro OGD model was employed in mouse BMECs to mimic brain hypoxic and ischemic conditions; MTT was used to determine cell viability. qRT-PCR was used to determine the expression of long non-coding RNA (lncRNA)-MALAT1 and miR-145 under OGD conditions; in vitro tube formation assay was used to investigate angiogenic effect of MALAT1 and miR-145 The relationship between lncRNA-MALAT1/ miR-145 and miR-145 /VEGF-A/ANGPT2 was evaluated by qRT-PCR and Western blot, and direct binding was assessed using dual luciferase assay. Results showed that the levels of lncRNA-MALAT1 and miR-145 were up-regulated in OGD-induced BMECs. miR-145 functioned as an anti-angiogenic and pro-apoptotic factor in OGD treated BMECs via down-regulating VEGF-A and ANGPT2 directly. While lncRNA-MALAT1 enhanced the expressions of VEGF-A and ANGPT2 by targetting miR-145 to promote angiogenesis and proliferation of BMECs under OGD conditions. Our present study revealed the inhibitory functions of miR-145 on angiogenesis through direct targetting on VEGF-A and ANGPT2 for the first time and proved the protective role of lncRNA-MALAT1 for BMECs under OGD conditions through the direct regulation of miR-145 ., (© 2019 The Author(s).)

Background: Hepatitis B virus X protein (HBx) plays a crucial role in initiating and promoting HBV-induced hepatocellular carcinoma (HCC) development. Reports indicated that HBx promotes cancer stem cell (CSC) generation, which may be associated with HBV-related HCC. Noncoding RNA miR-124 and long noncoding RNA (lncRNA)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) were considered to be involved deeply in the progress of HBx-related HCC. Hence, the underlying mechanism of miR-124 and lncRNA-MALAT1 in regulating HBx-promoted CSC needs to be studied., Materials and Methods: In present study, HepG2-X cell line was induced by transfect HBx into HepG2 cells. Overexpressing of miR-124 or silencing of lncRNA-MALAT1 was completed by transfecting miR-124 mimic or shMALAT1 into HepG2-X cells. HBx-induced CSC properties and tumorigenic potential of HepG2 cells were determined by detecting CSC marker expression, colony formation assay, and xenograft tumorigenesis. The mechanism of HBx-induced CSC properties was explored by PI3K/Akt inhibitor. Interaction of miR-124 and lncRNA-MALAT1 was detected by luciferase reporter assay., Results: HBx promoted CSC properties through upregulating stemness markers and reprogramming proteins, and contributed to tumorigenicity of HepG2-X cells both in vivo and in vitro. Inhibition of Akt activation blocked the HBx-stimulated reprogramming proteins and stemness markers. HBx upregulated lncRNA-MALAT1 expression while downregulating miR-124 expression in HepG2-X cells. miR-124 interacts with lncRNA-MALAT1 by direct targeting. Overexpression of miR-124 or silencing of lncRNA-MALAT1 both blocked HBx-induced CSC generation, stemness-related factor activation and tumorigenicity via PI3K/Akt signaling., Conclusion: Our results demonstrated that miR-124 interact with lncRNA-MALAT1 and involve in regulating HBx-induced CSC properties via PI3K/Akt signaling., (© 2018 Wiley Periodicals, Inc.)

To study the effect of small interfering RNA targeting metastasis-associated lung adenocarcinoma transcript1 (si-MALAT1) combining with curcumin on the invasion and migration abilities of human colon cancer SW480 cells, and to explore the involved molecular mechanism. The recombinant lentiviral vector expressing si-MALAT1 was constructed, and its titer was determined by gradient dilution method. The colon cancer SW480 cells with stable expression of si-MALAT1 was established, followed by treatment with curcumin at different concentrations. The effect of curcumin or si-MALAT1 alone and the combination of the two on the cell activity was detected by MTT assay. The cell invasion and migration abilities were detected by transwell and scratch-wound assay. The relative expression level of MALAT1 was detected by RT-qPCR. The protein expression was determined by Western blot analysis. The IC50 of curcumin alone was 77.69 mmol/L, which was 51.17 mol/L when combined with curcumin and random sequence. The IC50 of curcumin was 30.02 mmol/L when combined with si-MALAT1. The increased susceptibility multiples was 2.58. The wound healing rates were 30.9% and 67.5% after treatment with si-MALAT1 combined with curcumin for 24 hrs and 48 hrs, respectively. The numbers of invasion cells were 200±12, 162±13, 66±8, 53±4 and 16±3 after treatment with si-MALAT1 combined with curcumin for 48 hrs. The relative expression level of lncRNA-MALAT1 in the curcumin group was 68%, and the relative expression level of lncRNA-MALAT1 in si-MALAT1group was 56%, and that for the combination treatment group was about 21%. The protein expression levels of β- catenin, c-myc and cyclinD1 were significantly down-regulated upon treatment with certain concentration of si-MALAT1 alone or combined with curcumin.si-MALAT1 could significantly inhibit the invasion and migration of SW480 cells by enhancing the sensitivity of SW480 cells to curcumin. The mechanism involved mignt be related to the down-regulation of β-catenin, c-myc and cyclinD1 proteins.