Metastasis-associated Lung Adenocarcinoma Transcript 1 Expression Research Articles

Long non-coding RNA MALAT1 modulates myocardial ischemia-reperfusion injury through the PI3K/Akt/eNOS pathway by sponging miRNA-133a-3p to target IGF1R expression

The mechanism of myocardial ischemia-reperfusion injury (MIRI) is a complex pathophysiological process that can lead to poor patient outcomes. Although LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reported to be highly expressed in myocardial ischemia reperfusion (IR) injury, the specific mechanism remains largely unknown. This study aimed to elucidate the roles and possible mechanism of MALAT1 in myocardial IR injury. IR model was established in rats by ligation of the anterior descending artery in vivo, and H9c2 and HL-1 cells were treated by hypoxia/reoxygenation (HR) to construct the model in vitro. The small interfering RNA (siRNA) for MALAT1 and miR-133a-3p mimics, inhibitor was used to transfect the cells. The expression of MALAT1, miR-133a-3p in MIRI were evaluated using real-time quantitative polymerase chain reaction (qRT-PCR)，immunohistochemistry (IHC) and western blot (WB). Relationships between MALAT1, insulin-like growth factor 1 receptor (IGF1R) with miR-133a-3p were confirmed by luciferase reporter assay. Annexin V-FITC/PI double-labeled flow cytometry, terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Cell Counting Kit-8 (CCK-8), serum creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were evaluated to examine the impact of MALAT1 on MIRI. Our results revealed that MALAT1 was highly expressed, while miR-133a-3p and IGF1R were repressed in IR and HR groups. Knockdown of MALAT1 alleviate the pro-apoptotic effect and myocardial injury in vitro and in vivo. Systematically, MALAT1 may serve as a sponge for miR-133a-3p to suppress IGF1R, which a direct target of miR-133a-3p, then inhibit the PI3K/Akt/eNOS survival pathway. Mechanistically, our study demonstrated that MALAT1 regulates PI3K/Akt/eNOS signaling via miR-133a-3p. In summary, these results suggest that MALAT1 and miR-133a-3p play important roles in MIRI. MALAT1 regulates miR-133a-3p /IGF1R axis. These results show light on the underlying mechanisms of MIRI and provide potential therapeutic targets for MIRI.

LncRNA MALAT1/miR-143 axis is a potential biomarker for in-stent restenosis and is involved in the multiplication of vascular smooth muscle cells.

The purpose of this study is to observe the potential value and underlying mechanism of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-143 axis in ISR. A total of 150 participants were enrolled, including 100 patients (observation group) with coronary heart disease who underwent stent implantation in the Department of Cardiology of our hospital between January 2018 and January 2020, and 50 healthy people (control group) concurrently underwent a physical examination. Serum MALAT1 and miR-143 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Tumor necrosis factor-α (TNF-α; 10 ng/mL) induced human vascular smooth muscle cells (HVSMCs). MALAT1 increased while miR-143 decreased in the observation group versus the control group (P < 0.001). The non-restenosis group had significantly elevated MALAT1 expression while decreased miR-143 expression than the restenosis group (P < 0.001). The areas under the curves of the expression of MALAT1 and miR-143 in predicting restenosis were 0.917 and 0.881, respectively. Following si-MALAT1 transfection, HVSMC multiplication and invasiveness decreased significantly (P < 0.05). miR-143-inhibitor was observed to upregulate the luciferase activity of MALAT1-WT (P < 0.05). MALAT1 is highly expressed in patients with ISR while miR-143 is decreased, and the MALAT1/miR-143 axis is a potential pathway to modulate the multiplication and invasiveness of HVSMCs.

MALAT-1 Expression Correlates with Prognosis in Non-Small-Cell Lung Carcinoma: A Systematic Review and Meta-analysis.

Background Non-small-cell lung carcinoma (abbreviated as NSCLC) progresses rapidly and lacks appropriate biological markers. Recent studies have shown that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) has potential application value for clinically diagnosing lung carcinoma. Thus, this study conducted a systematic review and meta-analysis for assessing if MALAT-1 has a relationship to NSCLC outcome. Methods This study conducted the search of China National Knowledge Infrastructure, China Science and Technology Journal, SinoMed, EMBASE, Cochrane library, Web of Science, Wanfang database, and PubMed from inception to September, 1, 2021. The published article about MALAT-l expression for NSCLC patients was analyzed. We used combined hazard rates under the confidence interval of 95% for examining the relationship of MALAT-l and NSCLC.Results In this meta-analysis, we found that 10 studies were included, and MALAT-1 expressions were distinctly related to an unfavorable overall survival (HR: 2.34 (1.65, 3.33); I2 = 76%). Considering the merger's clinical heterogeneity, for meta-analysis, we used the random-effects method. Conclusion Overexpression of MALAT-1 showed correlations to the less effective outcome of NSCLC. MALAT-1 might be a new NSCLC prognosis marker.

MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p.

The aim of this study was to clarify the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in proliferation, migration, and invasion of malignant pleural mesothelioma (MPM) cells. The quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of MALAT1 in MPM cell lines. The effects of MALAT1 and miR-141-3p on the proliferation, migration, and invasion of MPM cells were studied through a series of in vitro cellular experiments. The flow cytometry was utilized to detect the cell apoptosis. The dual‐luciferase reporter assay was employed to explore the binding relationship among MALAT1, miR-141-3p, and YES-associated protein 1 (YAP1). MALAT1 was overexpressed in MPM cell lines, while its knockdown significantly inhibited the cell proliferation, migration, and invasion, and increased the number of MPM cells in the G0/G1 phase. In addition, MALAT1 could directly bind to miR-141-3p and inhibit its expression. YAP1 has been identified as a downstream target of miR-141-3p, and its expression level was inhibited by miR-141-3p. MALAT1 can be used as a competitive endogenous RNA (ceRNA) to regulate the YAP1-Hippo signaling pathway through miR-141-3p, promote the proliferation, migration, and invasion of MPM cells, and provide a new target for the therapy of MPM.

MALAT1 promotes liver fibrosis by sponging miR‑181a and activating TLR4‑NF‑κB signaling.

The aim of the present study was to investigate whether long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) could modulate activation and inflammation of hepatic stellate cell (HSCs) via regulation of a microRNA (miR)-181a-toll like receptor (TLR)4/nuclear factor (NF)-κB axis, thereby contributing to the development of liver fibrosis. A total of 151 patients with liver fibrosis were recruited, and the serum levels of alanine transaminase, aspartate aminotransferase and albumin were determined. Transforming growth factor (TGF)-β1 and LPS were used to activate and induce inflammation in the human HSC cell line LX2. MALAT1 was knocked using small interfering RNA or overexpressed, and an inhibitor and mimic of miR-181a-5p were used to examine the effect of MALAT1 and miR-181a-5p on the activation and inflammation of LX2 cells. Both MALAT1 and miR-181a-5p expression performed well in their ability to differentiate patients with liver fibrosis from healthy volunteers, and MALAT1 expression was associated with the severity of liver fibrosis. The expression levels of TLR4 and NF-κB were increased after stimulation with LPS or TGF-β1, but MALAT1 knockdown or miR-181a-5p mimic transfection abrogated this increase. Moreover, the TGF-β1-induced increase in viability, proliferation, migration, adhesion and collagen production, and the LPS-induced inflammation of LX2 cells were all reversed after MALAT1 knockdown or transfection with miR-181a-5p mimic. The MALAT1/miR-181a-5p axis was involved in regulating collagen production and inflammation by activating TLR4/NF-κB signaling, which may be conducive to liver fibrosis treatment in the future.

LncRNA MALAT1 Promotes Tumor Angiogenesis by Regulating MicroRNA-150-5p/VEGFA Signaling in Osteosarcoma: In-Vitro and In-Vivo Analyses.

The present study aims to analyze the expression of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in human osteosarcoma (OS) cells and to investigate its role in OS-induced angiogenesis. MALAT1 expression in OS cells was significantly higher than in normal osteoblasts. The functional analysis indicated that MALAT1 appears to enhance OS-induced angiogenesis, in vitro and in vivo analyses, endothelial cell proliferation and migration, chick embryo angiogenesis assay, and zebrafish xenograft model. Mechanistically, silencing MALAT1 downregulated vascular endothelial growth factor A (VEGFA) expression and upregulated miR-150-5p expression in OS cells, and MALAT1-mediated angiogenic induction by VEGFA in OS microenvironment. Moreover, MALAT1 directly targeted miR-150-5p and miR-150-5p directly target VEGFA in OS. Overexpression of miR-150-5p downregulates VEGFA expression in OS. More notably, we showed that MALAT1 induced angiogenesis in OS microenvironment by upregulating the expression of VEGFA via targeting miR-150-5p. Overall, our findings suggest that MALAT1 promotes angiogenesis by regulating the miR-150-5p/VEGFA signaling in OS microenvironment. The findings of the molecular mechanisms of MALAT1 in tumor angiogenesis offer a new viewpoint on OS treatment.

Long non-coding RNA MALAT1 silencing elevates microRNA-26a-5p to ameliorate myocardial injury in sepsis by reducing regulator of calcineurin 2

ObjectiveSepsis is a leading cause of morbidity and mortality after surgery. We aimed to explore the role of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) sponging microRNA-26a-5p in sepsis-induced myocardial injury by regulating regulator of calcineurin 2 (Rcan2). MethodsHL-1 cells were incubated with lipopolysaccharide (LPS) to induce in vitro cardiomyocyte injury models, which were then treated with silenced MALAT1 vector, miR-26a-5p mimic or Rcan2 overexpression vector. Next, inflammatory factor level and apoptosis of cells were determined. The in vivo mouse models were constructed by intraperitoneal injection of LPS. The modeled mice were injected with relative oligonucleotides and the pathology, apoptosis, and inflammation in mouse myocardial tissues were assessed. Expression of MALAT1, miR-26a-5p and Rcan2 in vivo and in vitro was evaluated. ResultsMALAT1 and Rcan2 were upregulated while miR-26a-5p was downregulated in LPS-treated HL-1 cells and mice. MALAT1 silencing or miR-26a-5p upregulation suppressed LPS-induced inflammation and apoptosis of cardiomyocytes in cellular and animal models. These effects of elevated miR-26a-5p could be reversed by upregulating Rcan2, and MALAT1 knockdown-induced ameliorative impacts could be reversed by miR-26a-5p downregulation. ConclusionMALAT1 silencing elevated miR-26a-5p to ameliorate LPS-induced myocardial injury by reducing Rcan2. Our research may provide novel biomarkers for the treatment of sepsis.

Pancreatic Cancer Progression Is Regulated by IPO7/p53/LncRNA MALAT1/MiR-129-5p Positive Feedback Loop.

Background: Pancreatic cancer is a malignancy with poor prognosis. Importin 7 (IPO7) is a soluble nuclear transport factor, which has been linked to the pathogenesis of several human diseases. However, its role and underlying mechanism in pancreatic cancer are still obscure.Methods: Immunohistochemical staining and quantitative real-time polymerase chain reaction (qPCR) were performed to determine IPO7 expression in pancreatic cancer tissues and adjacent tissues. Western blot was used to measure IPO7 expression at the protein level in cell lines. Cell Counting Kit-8 (CCK-8), 5-bromo-2′-deoxyuridine (BrdU), flow cytometry, and Transwell assays were employed to explore the biological functions of IPO7. Subcutaneous xenograft transplanted tumor model and caudal vein injection model in mice were also established to validate the oncogenic role of IPO7. Western blot and qPCR were utilized to detect the regulatory function of IPO7 on p53 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), respectively. Interaction between MALAT1 and miR-129-5p and interaction between miR-129-5p and IPO7 were verified by bioinformatics prediction, qPCR, dual-luciferase reporter gene experiment, RNA immunoprecipitation (RIP), and pull-down assay.Results: Upregulation of IPO7 in pancreatic cancer tissues was associated with adverse prognosis of the patients with pancreatic cancer. Knocking down IPO7 remarkably suppressed cancer cell proliferation and metastasis, while it promoted apoptosis. Overexpression of IPO7 facilitated the malignant phenotypes of pancreatic cancer cells. Mechanistically, IPO7 could repress the expression of p53 and induce the expression of MALAT1 but reduce miR-129-5p expression. Furthermore, miR-129-5p was identified as a posttranscriptional regulator for IPO7, and its inhibition led to IPO7 overexpression in pancreatic cancer cells.Conclusion: IPO7 is a novel oncogene for pancreatic cancer, and IPO7/p53/MALAT1/miR-129-5p positive feedback loop facilitates the progression of this deadly disease.

MALAT-1 is Associated with the Doxorubicin Resistance in U-2OS Osteosarcoma Cells.

PurposeOur study aimed to investigate the relationship between MALAT-1 (metastasis-associated lung adenocarcinoma transcript 1) expression and the chemotherapy drug resistance in osteosarcoma.MethodsThe U-2OS osteosarcoma cell line was selected for the experiment. The cells were treated with methotrexate, doxorubicin, cisplatin, and ifosfamide, respectively. RT-PCR was applied to detect the MALAT-1 expression in cells. The doxorubicin-resistant cell line was constructed. The cells were divided into doxorubicin-sensitivity group (DS/shCtrl), doxorubicin-resistance group (DR/shCtrl) and shMALAT1-doxorubicin-resistance group (DR/shMALAT1). The colony formation assay and 5-ethynyl-2ʹ-deoxyuridine (EdU) assay were used to detect cell proliferation. PI staining was used to detect the cell cycle. Transwell assay and wound healing assay were used to observe the migration and invasion ability. Annexin V-FITC assay was used to detect cell apoptosis. Western blot was used to detect the protein expression and potential mechanism. The impacts of MALAT-1 expression were verified in vivo.ResultsThe MALAT-1 was upregulated in the doxorubicin-resistant U-2OS osteosarcoma cells. Downregulating MALAT-1 in the doxorubicin-resistant cells inhibited the proliferation, migration, and invasiveness, increased the ratio of cells in the G0/G1 phase, promoted apoptosis. In the doxorubicin-resistant U-2OS cells, the extracellular regulated protein kinases (ERK) phosphorylation was declined, which could be reversed by downregulating MALAT-1. In vivo assay indicated that the growth of doxorubicin-resistant solid osteosarcoma could be suppressed by downregulating MALAT-1.ConclusionOur study provides evidence that doxorubicin may upregulate MALAT-1 in osteosarcoma. Downregulating MALAT-1 in the doxorubicin resistance U-2OS cells could reverse the resistance and may improve chemotherapeutic efficiency. Some conclusions in previous literature may be one-sided.

Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promotes the Osteoblast Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Targeting the microRNA-96/Osterix Axis.

To investigate whether and how the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) sponges microRNA-96 (miR-96) to achieve the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Protein levels were detected by Western blot. Mineralized bone matrix formation was studied by alizarin red staining. Metastasis-associated lung adenocarcinoma transcript 1, miR-96, and osteogenesis-related Messenger RNA expression was assessed by Quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The interactions between miR-96 and osterix (Osx), MALAT1, and miR-96 were determined by luciferase reporter assay. The expression of MALAT1 was upregulated whereas that of miR-96 was downregulated in osteogenic hBMSCs. In addition, the expression of MALAT1 significantly decreased whereas that of miR-96 increased in the hBMSCs of osteoporosis (OP) patients. qRT-PCR and alizarin red staining assays showed that MALAT1 silencing or miR-96 overexpression inhibits hBMSC osteogenic differentiation and vice versa. overexpression of miR-96 reversed the promotive effect of MALAT1 on the osteogenic differentiation of hBMSCs. Dual luciferase report assay verified that miR-96 is a regulatory target of MALAT1 and that Osx is a gene target of miR-96. Taken together, the results demonstrate that MALAT1 promotes the osteogenic differentiation of hBMSCs by regulating the miR-96/Osx axis. Our study provides novel mechanistic insights into the critical role of lncRNA MALAT1 as a microRNA sponge in OP patients and sheds new light on lncRNA-directed diagnostics and therapeutics in OP.

Increased MALAT1 expression predicts poor prognosis in primary gastrointestinal diffuse large B-cell lymphoma.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the pathogenesis and progression of several cancers. However, the potential effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in patients with PGI-DLBCL. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably upregulated in PGI-DLBCL tissues compared to paired adjacent non-tumor tissues (P < 0.001), and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.838. MALAT1 expression was further increased in the non-germinal center B-cell-like (non-GCB), advanced stage (stages IIE-IV) and International Prognostic Index (IPI) score (3-5) groups (P = 0.01, P < 0.001 and P < 0.001, respectively). Furthermore, Kaplan-Meier analysis showed that elevated MALAT1 expression correlated with inferior overall survival (OS) and progression-free survival in PGI-DLBCL patients (P < 0.001 and P < 0.001, respectively), and our multivariate analysis results suggested that upregulation of MALAT1 and high IPI score (3-5) were two unfavorable prognostic factors for PGI-DLBCL. In conclusion, our results demonstrate that MALAT1 may serve as a novel prognostic biomarker and an ideal therapeutic target for patients with PGI-DLBCL.

Long Noncoding RNA MALAT1 Interacts with miR-124-3p to Modulate Osteosarcoma Progression by Targeting SphK1.

Introduction Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological functions, including tumor proliferation, apoptosis, progression, and metastasis. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in various cancers, as well as osteosarcoma (OS); however, its underlying mechanism in OS is poorly understood. This investigation aims to elucidate the mechanisms of MALAT1 in OS proliferation and migration and to provide theoretical grounding for further targeted therapy in OS. Methods In the present study, we applied qRT-PCR to assess the MALAT1 expression in OS tissues and cell lines. The effects of MALAT1 and miR-124-3p on OS cell proliferation and migration were studied by CCK-8 and scratch assays. Cell cycle and apoptosis were tested using a flow cytometer. The competing relationship between MALAT1 and miR-124-3p was confirmed by dual-luciferase reporter assay. Results MALAT1 was overexpressed in OS cell lines and tissue specimens, and knockdown of MALAT1 significantly inhibited cell proliferation and migration and increased cell apoptosis and the percentage of G0/G1 phase. Furthermore, MALAT1 could directly bind to miR-124-3p and inhibit miR-124-3p expression. Moreover, MALAT1 overexpression significantly relieved the inhibition on OS cell proliferation mediated by miR-124-3p overexpression, which involved the derepression of sphingosine kinase 1 (SphK1). Conclusions We propose that lncRNA MALAT1 interacts with miR-124-3p to modulate OS progression by targeting SphK1. Hence, we identified a novel MALAT1/miR-124-3p/SphK1 signaling pathway in the regulation of OS biological behaviors.

MALAT1: A Pivotal lncRNA in the Phenotypic Switch of Gastric Smooth Muscle Cells via the Targeting of the miR-449a/DLL1 Axis in Diabetic Gastroparesis.

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). Our previous study suggested that the expression of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is closely related to DGP. However, the role of MALAT1 in DGP pathogenesis remains unclear. Here, we aim to characterize the role of MALAT1 in DGP. First, we analyzed the lncRNA expression profiles through lncRNA sequencing. Next, we detected MALAT1 expression in the stomach tissues of DGP model mice and diabetic patients. Then, we investigated the role and mechanisms of MALAT1 in the proliferation, migration, phenotypic switch, and carbachol-induced intracellular Ca2+ changes in human gastric smooth muscle cells (HGSMCs) under high glucose (HG) conditions, using short hairpin RNA technology, RNA immunoprecipitation, and dual-luciferase reporter assays. We show that MALAT1 expression was upregulated in the gastric tissues of DGP model mice, the adjacent healthy tissues collected from diabetic gastric cancer patients with DGP symptoms, and in HGSMCs cultured under HG conditions. Functionally, MALAT1 knockdown in vitro impacted the viability, proliferation, migration and promoted the phenotypic switch of HGSMCs under HG conditions. Additionally, we show that MALAT1 sponged miR-449a, regulating Delta-like ligand 1 (DLL1) expression in HGSMCs; any disturbance of the MALAT1/miR-449a/DLL1 pathway affects the proliferation, migration, phenotypic switch, and carbachol-induced Ca2+ transient signals in HGSMCs under HG conditions. Collectively, our data highlight a novel regulatory signaling pathway, the MALAT1/miR-449a/DLL1 axis, in the context of DGP.

Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3\u03b2 axis

BackgroundPropofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β).MethodsC57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured.ResultsOur experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression.ConclusionOverall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

Mechanism of tumor‑derived extracellular vesicles in regulating renal cell carcinoma progression by the delivery of MALAT1.

Renal cell carcinoma (RCC) is a major healthcare burden globally. Tumor-derived extracellular vesicles (EVs) contribute to the formation of a pro-metastatic microenvironment. In the present study, we explored the role and mechanism of RCC cell 786-O-derived EVs (786-O-EVs) in RCC. First, 786-O-EVs were extracted and identified, and EV internalization of RCC cells was observed. RCC cell malignant behaviors and long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression patterns were detected before and after 786-O-EV treatment. MALAT1 was intervened to evaluate RCC cell behaviors. The downstream mechanism involving MALAT1 was predicted. In addition, the relationship among MALAT1, transcription factor CP2 like 1 (TFCP2L1) and ETS proto-oncogene 1, transcription factor (ETS1) was analyzed. TFCP2L1 expression patterns were measured after 786-O-EV exposure. Tumor xenograft formation assay and lung metastasis model were adopted to verify the role of 786-O-EVs in vivo in RCC. It was found that 786-O-EVs could be internalized by RCC cells. 786-O-EVs promoted RCC cell malignant behaviors, accompanied by elevated MALAT1 expression levels. The 786-O-EVs with MALAT1 knockdown attenuated the promotive effect of sole 786-O-EVs on RCC cells. MALAT1 located ETS1 in the TFCP2L1 promoter and negatively regulated TFCP2L1, and ETS1 protein could specifically bind to MALAT1. 786-O-EVs enhanced the binding of ETS1 and the TFCP2L1 promoter and decreased TFCP2L1 expression. In vivo, 786-O-EVs promoted tumor growth and RCC lung metastasis, which was suppressed following inhibition of MALAT1. Our findings indicated that 786-O-EVs promoted RCC invasion and metastasis by transporting MALAT1 to promote the binding of transcription factor ETS1 and TFCP2L1 promoter.

Combined Impacts of Genetic Variants of Long Non-Coding RNA MALAT1 and the Environmental Carcinogen on the Susceptibility to and Progression of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, and long non-coding (lnc)RNA of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was recently reported to play a crucial role in OSCC development and progression. However, potential effects of genetic variants of MALAT1 on the development of OSCC are still unclear. Herein, we performed a case-control study in 1350 patients with OSCC and 1199 healthy controls to evaluate the association between functional single-nucleotide polymorphisms (SNPs) of MALAT1 and OSCC susceptibility, as well as its clinicopathologic characteristics. A TaqMan allelic discrimination assay was used to genotype four tagging SNPs, viz., rs3200401 C>T, rs619586 A>G, rs1194338 C>A, and rs7927113 G>A, and results showed that the MALAT1 rs3200401 T allele had a lower risk of OSCC (adjusted odds ratio (AOR): 0.779, 95% confidence interval (CI): 0.632~0.960, p=0.019) and a higher risk of developing moderately (grade II)/poorly (grade III) differentiated OSCC (AOR: 1.508-fold, 95% CI: 1.049~2.169, p=0.027) under a dominant model. According to environmental carcinogen exposure, patients with a betel quid-chewing habit who carried the T allele of rs3200401 more easily developed high-grade (II/III) OSCC (AOR: 1.588, 95% CI: 1.055~2.390, p=0.027), and patients with the same genotype but who did not chew betel quid had a lower risk of developing lymph node metastasis (AOR: 0.437, 95% CI: 0.255~0.749, p=0.003). In addition to rs3200401, the rs619586 AG/GG genotype was associated with increased risks of developing advanced stages (III+IV) and larger tumor sizes (>T2) compared to the AA genotype, especially in the subgroup of betel quid chewers. Furthermore, analyses of clinical datasets revealed that the MALAT1 expression level was upregulated in OSCC compared to normal tissues, especially in the betel quid-chewing population. These results indicated involvement of MALAT1 SNPs rs3200401 and rs619586 in the development of OSCC and support the interaction between MALAT1 gene polymorphisms and the environmental carcinogen as a predisposing factor for OSCC progression.

Propofol attenuates renal ischemia/reperfusion injury by regulating the MALAT1/miR-126-5p axis.

Propofol (PPF) plays a protective role in ischemia-reperfusion (I/R) in multiple organs, including renal ischemia-reperfusion injury (RIRI). The present study aimed to investigate the underlying mechanisms by which PPF exerts its protective functions in RIRI. BALB/c mice were employed for the construction of RIRI animal model. PPF pre-treatment was carried out before I/R. An in vitro I/R model was established with HK-2 cells after hypoxia/reoxygenation (H/R) culture, and PPF was utilized to treat the cells before H/R. A quantitative-polymerase chain reaction (qPCR) was conducted to detect long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-126-5p expression levels. Flow cytometry was adopted to detect the apoptosis of HK-2 cells. Bioinformatics analysis, qPCR, a luciferase reporter gene experiment and a RNA immunoprecipitation experiment were used to determine the regulatory relationship between MALAT1 and miR-126-5p. The expression level of vascular endothelial growth factor A (VEGFA) was examined by western blotting. MALAT1 expression was augmented and miR-126-5p was decreased in RIRI models. PPF pre-treatment remarkably reduced creatinine and urea nitrogen levels in the serum of BALB/c mice with RIRI, and diminished the apoptosis of HK-2 cells treated with H/R. In addition, PPF pre-treatment markedly restrained the expression of MALAT1 in both in vivo and in vitro models and up-regulated miR-126-5p expression. MALAT1 could adsorb miR-126-5p to repress it and up-regulate VEGFA. MALAT1 overexpression reversed the protective effects of PPF on RIRI. PPF protects the kidney against RIRI by inhibiting MALAT1 and up-regulating miR-126-5p expression, as well as indirectly inhibiting the expression of VEGFA.

Biochemical study on long non coding RNA gene expression in women having preeclampsia

BackgroundPreeclampsia (PE) is a familiar gestational complication that affects 3% to 5% of pregnant women. After 20 weeks of pregnancy, PE typically presents as new-onset hypertension and proteinuria. Inadequate trophoblast invasion, accompanied by defects in placental vasculature formation and subsequent placental underperfusion, has been linked to the pathology of PE. Via changes in the biological functions of trophoblasts, lncRNAs may influence the occurrence and progression of PE. ObjectivesThe objective of this research is to see whether the levels of expression of Metastasis-associated lung adenocarcinoma transcript1 (MALAT1) and SPRY4 intronic transcript 1 (SPRY4-IT1) are linked to preeclampsia susceptibility and pathogenesis. Subjects and methodsA total of 195 people took part in this report. A hundred and thirty were patients with preeclampsia (65 mild and 65 severe Preeclampsia). The control group contained 65 normally pregnant women. Both groups had similar age. All groups were subjected to (complete history taking focusing on age, parity and past history of hypertension or diabetes mellitus) thorough clinical examination. The Determination of MALAT1 and SPRY4-IT1 expression levels in placental tissue have been performed by real time q PCR technique. Results showedMALAT1 and SPRY4-IT1 expression levels were found to vary significantly between the studied groups, with lower MALAT1 and higher SPRY4-IT1 expression levels in Preeclampsia patients than in controls. ConclusionFrom this study, it could be concluded that Malat1 and SPRY4-IT1 expression levels might be used as predicting markers for pathogenesis and diagnosis of preeclampsia.

Si-MALAT1 attenuates thymic cancer cell proliferation and promotes apoptosis via the miR-145-5p/HMGA2 pathway.

Metastasis-associated-lung-adenocarcinoma-transcript-1 (MALAT1) is a long non-coding RNA that is considered a potential tumor marker. The present study aimed to investigate the effect and mechanism of MALAT1 on cell proliferation and apoptosis in thymic cancer cells. IU-TAB-1, A549, HCT-116 and 293T cells were screened by reverse transcription-quantitative PCR to assess high-mobility group AT-hook 2 (HMGA2) expression in various types of cancer cells and were transfected with small interfering (si)RNA targeting MALAT1 (si-MALAT1). Cell proliferation was evaluated by Cell Counting Kit-8 assay. Cell apoptosis and cell cycle were examined using flow cytometry. The protein expression of cyclin D1, cyclin E, Bax, Bcl-2 and HMGA2 was determined by western blot analysis, while the associations between MALAT1 and microRNA (miR)-145-5p and between HMGA2 and miR-145-5p were determined by luciferase reporter assay. Among the four cell lines evaluated, IU-TAB-1 showed the highest expression of MALAT1; thus, IU-TAB-1 cells were selected for subsequent experiments. Compared with the findings in the control group, si-MALAT1 significantly decreased the cell proliferation of IU-TAB-1 cells, whereas the apoptosis levels and number of cells in G2 phase were increased. The protein expression levels of cyclin D1, cyclin E, Bcl-2 and HMGA2 were significantly decreased in the si-MALAT1 group compared with those in the control group, while Bax levels were significantly increased. After treatment with si-MALAT1 in combination with miR-145-5p mimics or inhibitors, cell proliferation and apoptosis were respectively enhanced and inhibited in IU-TAB-1 cells. miR-145-5p inhibited the luciferase activity of IU-TAB-1 cells transfected with the MALAT1 or HMGA2 3′ untranslated region. In conclusion, si-MALAT1 significantly attenuated cell proliferation and apoptosis via the miR-145-5p/HMGA2 pathway in thymic cancer cells.

Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145.

BackgroundThe long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells in vitro in vivo.MethodsThe Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice.ResultsThe expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P<0.001; F=2.268, t=15.859, P<0.001). Knockdown of MALAT1 reduced the migratory and invasive capabilities of PCa cells (F=0.017, t=12.212, P<0.001; F=10.723, t=6.016, P=0.002). Using direct binding, MALAT1 suppressed the antitumor function of miR-145, which in turn upregulated transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) via SMAD3 and TGFBR2 (F=2.097, t=5.389, P=0.006; F=1.306, t=4.155, P=0.014).ConclusionsWe confirmed that MALAT1 acts as a competing endogenous RNA (ceRNA) of miR-145. The MALAT1 based regulation of MiR-145-5p-SMAD3/TGFBR2 interactions could be an intriguing molecular pathway for the progression of PCa.