MALAT1 Expression Research Articles

The effect of bone marrow mesenchymal stromal cell exosomes on acute myeloid leukemia’s biological functions: a focus on the potential role of LncRNAs

Acute myeloid leukemia represents a group of malignant blood disorders that originate from clonal over-proliferation and the differentiation failure of hematopoietic precursors, resulting in the accumulation of blasts in the bone marrow. Mesenchymal stromal cells (MSCs) have been shown to exert diverse effects on tumor cells through direct and indirect interaction. Exosomes, as one of the means of indirect intercellular communication, are released from different types of cells, including MSCs, and their various contents, such as lncRNAs, enable them to exert significant impacts on target cells. Our study aims to investigate the effects of BM-MSC exosomes on the cellular and molecular characterization of HL-60 AML cells, particularly detecting the alterations in the expression of lncRNAs involved in AML leukemogenesis, cell growth, drug resistance, and poor prognosis. BM-MSCs were cultured with serum-free culture media to isolate exosomes from their supernatants. The validation of exosomes was performed in three stages: morphological analysis using TEM, size evaluation using DLS, and CD marker identification using flow cytometry. Subsequently, the HL-60 AML cells were treated with isolated BM-MSC exosomes to determine the impact of their contents on leukemic cells. Cell metabolic activity was evaluated by the MTT assay, while cell cycle progression, apoptosis, ROS levels, and proliferation were assessed by flow cytometry. Furthermore, RT-qPCR was conducted to determine the expression levels of lncRNAs and apoptosis-, ROS-, and cell cycle-related genes. MTT assay and flow cytometry analysis revealed that BM-MSC exosomes considerably suppressed cell metabolic activity, proliferation, and cell cycle progression. Also, these exosomes could effectively increase apoptosis and ROS levels in HL-60 cells. The expression levels of p53, p21, BAX, and FOXO4 were increased, while the BCL2 and c-Myc levels decreased. MALAT1, HOTAIR, and H19 expression levels were also significantly decreased in treated HL-60 cells compared to their untreated counterparts. BM-MSC exosomes suppress cell cycle progression, proliferation, and metabolic activity while simultaneously elevating the ROS index and apoptosis ratio in HL-60 cells, likely by reducing the expression levels of MALAT1, HOTAIR, and H19. These findings suggest that BM-MSC exosomes might serve as potential supportive therapies for leukemia.

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

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

Long Noncoding RNA MALAT1: Salt-Sensitive Hypertension.

Hypertension stands as the leading global cause of mortality, affecting one billion individuals and serving as a crucial risk indicator for cardiovascular morbidity and mortality. Elevated salt intake triggers inflammation and hypertension by activating antigen-presenting cells (APCs). We found that one of the primary reasons behind this pro-inflammatory response is the epithelial sodium channel (ENaC), responsible for transporting sodium ions into APCs and the activation of NADPH oxidase, leading to increased oxidative stress. Oxidative stress increases lipid peroxidation and the formation of pro-inflammatory isolevuglandins (IsoLG). Long noncoding RNAs (lncRNAs) play a crucial role in regulating gene expression, and MALAT1, broadly expressed across cell types, including blood vessels and inflammatory cells, is also associated with inflammation regulation. In hypertension, the decreased transcriptional activity of nuclear factor erythroid 2-related factor 2 (Nrf2 or Nfe2l2) correlates with heightened oxidative stress in APCs and impaired control of various antioxidant genes. Kelch-like ECH-associated protein 1 (Keap1), an intracellular inhibitor of Nrf2, exhibits elevated levels of hypertension. Sodium, through an increase in Sp1 transcription factor binding at its promoter, upregulates MALAT1 expression. Silencing MALAT1 inhibits sodium-induced Keap1 upregulation, facilitating the nuclear translocation of Nrf2 and subsequent antioxidant gene transcription. Thus, MALAT1, acting via the Keap1-Nrf2 pathway, modulates antioxidant defense in hypertension. This review explores the potential role of the lncRNA MALAT1 in controlling the Keap1-Nrf2-antioxidant defense pathway in salt-induced hypertension. The inhibition of MALAT1 holds therapeutic potential for the progression of salt-induced hypertension and cardiovascular disease (CVD).

Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment.

African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.

Regulatory role of lncRNA MALAT1 and miR-150-3p interaction in breast cancer progression and therapeutic implications

Long non-coding RNAs (lncRNAs) play crucial roles in cancer progression and metastasis. However, the precise regulatory mechanisms of MALAT1, an lncRNA, in breast cancer remain elusive. Consequently, this study explored the specific role of MALAT1 as a tumor promoter in breast cancer. Initially, MALAT1-small interfering RNA (siRNA) transfection resulted in the inhibition of breast cancer cell migration, colony formation, and invasion. Real-time polymerase chain reaction analysis also revealed increased E-cadherin expression and decreased vimentin and vascular endothelial growth factor (VEGF) mRNA levels subsequent to the transfection. Bioinformatic analysis further uncovered a specific interaction between MALAT1 and miR-150-3p, indicating elevated MALAT1 expression in breast cancer with a negative correlation to miR-150-3p expression. Furthermore, the overexpression of MALAT1 markedly suppressed miR-150-3p expression, indicating a reciprocal inhibition between the two. Luciferase reporter assays confirmed the specific association between miR-150-3p and MALAT1 at the sequence level. Furthermore, transfection with miR-150-3p mimic inhibited breast cancer cell migration, colony formation, and invasion, along with increased E-cadherin expression and decreased Vimentin and VEGF mRNA levels. Conversely, miR-150-3p inhibitor transfection led to opposing effects, reducing E-cadherin expression, and elevating vimentin and VEGF mRNA levels, while also inhibiting migration, colony formation, and invasion. Functionally, MALAT1 siRNA restrained breast cancer cell proliferation and migration while enhancing cellular apoptosis on administration to breast cancer cells, primarily mediated through miR-150-3p. Our findings delineate MALAT1 as a tumor growth-promoting gene antagonized by miR-150-3p. Building on these insights, this study proposes a potential therapeutic avenue for breast cancer treatment.

Identification and bioinformatics analysis of lncRNAs in serum of patients with ankylosing spondylitis

ObjectivesThe aim of this study was to explore the long non-coding RNA (lncRNA) expression profiles in serum of patients with ankylosing spondylitis (AS). The role of these lncRNAs in this complex autoimmune situation needs to be evaluated.MethodsWe used high-throughput whole-transcriptome sequencing to generate sequencing data from three patients with AS and three normal controls (NC). Then, we performed bioinformatics analyses to identify the functional and biological processes associated with differentially expressed lncRNAs (DElncRNAs). We confirmed the validity of our RNA-seq data by assessing the expression of eight lncRNAs via quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 AS and 20 NC samples. We measured the correlation between the expression levels of lncRNAs and patient clinical index values using the Spearman correlation test.ResultsWe identified 72 significantly upregulated and 73 significantly downregulated lncRNAs in AS patients compared to NC. qRT-PCR was performed to validate the expression of selected DElncRNAs; the results demonstrated that the expression levels of MALAT1:24, NBR2:9, lnc-DLK1-35:13, lnc-LARP1-1:1, lnc-AIPL1-1:7, and lnc-SLC12A7-1:16 were consistent with the sequencing analysis results. Enrichment analysis showed that DElncRNAs mainly participated in the immune and inflammatory responses pathways, such as regulation of protein ubiquitination, major histocompatibility complex class I-mediated antigen processing and presentation, MAPkinase activation, and interleukin-17 signaling pathways. In addition, a competing endogenous RNA network was constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs (MALAT1:24 and NBR2:9). We further found the expression of MALAT1:24 and NBR2:9 to be positively correlated with disease severity.ConclusionTaken together, our study presents a comprehensive overview of lncRNAs in the serum of AS patients, thereby contributing novel perspectives on the underlying pathogenic mechanisms of this condition. In addition, our study predicted MALAT1 has the potential to be deeply involved in the pathogenesis of AS.

Retracted] The AMPK‑mTOR axis requires increased MALAT1 expression for promoting granulosa cell proliferation in endometriosis.

[This retracts the article DOI: 10.3892/etm.2020.9453.].

Melatonin inhibits tongue squamous cell carcinoma: Interplay of ER stress-induced apoptosis and autophagy with cell migration

Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells. Western blot analysis showed the down-regulate of cyclin B1 and the up-regulate P21 protein by MT. MT was also shown to down-regulate the expression of Zeb1, Wnt5A/B, and β-catenin protein and up-regulate E-cadherin to inhibit the migration of CRL-1623 cells. MT also promoted the expression of ATF4, ATF6, Bip, BAP31 and CHOP in CRL-1623 cells leading to endoplasmic reticulum stress, and induced autophagy and apoptosis in CRL-1623 cells. Western blots showed that MT could promote the expression of Bax, LC3, and Beclin1 proteins and inhibit the expression of p62. We screened differentially expressed long non-coding RNAs (lncRNAs) in MT-treated cells and found that the expression of MALAT1 and H19 decreased. Moreover, MT inhibited tumor growth in nude mice inoculated with CRL-1623 cells. These results suggest that MT could induce autophagy, promote apoptosis, and provide a potential natural compound for the treatment of TSCC.

LncRNA MALAT1 suppresses monocyte-endothelial cell interactions by targeting miR-30b-5p and enhancing ATG5-mediated autophagy

BackgroundMonocyte-endothelial cell (EC) interactions are one of the earliest events in the development of atherosclerosis and play a crucial role in atherosclerotic plaque formation. Although attempts have been made to modulate this interaction, the underlying molecular signalling mechanisms remain unclear. This study aimed to investigate the role of long non-coding RNA MALAT1 in monocyte-EC interactions. MethodsThe expression of MALAT1, ICAM-1, VCAM-1, P-selectin, CCL2 and CXCL1 was evaluated in ApoE-/- mouse aortic tissues and inflamed human umbilical vein endothelial cells (HUVECs). The regulatory impact of MALAT1 on cell adhesion molecules, monocyte-EC adhesion, and autophagy was assessed. The interactions between MALAT1 and microRNAs (miRNAs) were evaluated using dual-luciferase reporter and RNA pull-down assays. ResultsMALAT1 expression decreased in ApoE-/- mouse aortic tissues and inflammatory HUVECs. MALAT1 overexpression suppressed the expression of ICAM-1, VCAM-1 and CXCL1, and reduced the migration and adhesion of monocytes to ECs. Inhibition of MALAT1 promoted cell adhesion molecule expression and monocyte-EC interactions. Mechanistically, MALAT1 binds directly to miR-30b-5p and decreases its effective expression by functioning as an endogenous sponge, thereby increasing the expression of autophagy-related gene 5 (ATG5) and stimulates endothelial autophagy. ConclusionsOur findings suggest that MALAT1 suppresses monocyte-EC interactions by targeting miR-30b-5p and enhancing ATG5-mediated endothelial autophagy. These data imply that MALAT1 may play a protective role at the early stages of the atherosclerotic process.

Abstract 2997: Identification of novel long non-coding RNAs in mantle cell lymphoma patients

Abstract Mantle Cell Lymphoma (MCL) is a rare and incurable type of B-cell non-Hodgkin lymphoma that affects about 4,000 people per year in the United States. Despite intense research to identify novel therapeutic approaches, the median progression-free survival after first-line treatment is four years. For this reason, the discovery of novel therapeutic targets remains crucial. Over half of the human genome is actively transcribed as non-coding RNAs. Among them, the non-coding RNAs that are longer than 200 nucleotides are named long non-coding RNAs (lncRNAs). lncRNAs have been shown to play essential roles in several human diseases, including cancer, by modulating cell cycle, immune response, or stemness through their interactions with DNA, protein, and RNA. For this reason, we decided to perform an RNA sequencing (RNA-Seq) profiling to identify the dysregulated lncRNAs in MCL. In more detail, we performed RNA-Seq in a cohort of 18 MCL patients compared to normal B-cells from the peripheral blood of healthy donors (HD). Reads were first trimmed for quality filtering, and adapters were removed using Trim Galore. Trimmed reads were mapped to the human genome (HG38 assembly) using HISAT 2. All the reads mapped inside the genomic coordinates of lncRNAs, reported in the GTF annotation file of GENCODE v43, were counted by featureCounts. Differential expression analysis between MCL samples vs HD was performed by LIMMA. To validate the results obtained from our internal MCL cohort, we also downloaded publicly available RNA-Seq data of 16 MCL patients and analyzed them using the previously described pipeline. Our analyses revealed several dysregulations in lncRNA expression occurring in MCL. Precisely, we identified 385 upregulated and 387 downregulated lncRNAs (|log2FC| > 0.58 and adjusted p-value < 0.05) in our internal MCL cohort, and 63% of them were also confirmed in the external cohort. Notably, the lncRNA called MALAT1 showed the highest significant upregulation in both cohorts, reinforcing this lncRNA's pivotal role in cancer development. To study the potential involvement of MALAT1 in MCL, we compared the MCL samples with higher MALAT1 expression (upper quartile) against those with lower expression (lower quartile) in both cohorts. The identified differentially expressed genes were used as input for a mechanistic network-based topological pathway analysis using MITHrIL. The analysis revealed that the KEGG pathway "Cell Cycle" was among the top upregulated pathways in MCL samples with high MALAT1 expression, suggesting the relevance of this lncRNA in promoting cellular proliferation, as also reported in the literature for other tumor types. In conclusion, our is the first study to describe the novel dysregulation signature of lncRNAs in MCL in two independent cohorts. Citation Format: Alessandro LaFerlita, Satishkumar Singh, Anuvrat Sircar, Robert Baiocchi, Natarajan Muthusamy, Lapo Alinari, Narendranath Epperla, Lalit Sehgal. Identification of novel long non-coding RNAs in mantle cell lymphoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2997.

MiR-122-IGF-1R signaling allied through the dysregulated lncRNA MALAT-1 expression in gastric carcinoma

MALAT-1 is extremely elevated in human malignancies thus functions as a prognostic biomarker. Nevertheless, limited data has been discovered concerning MALAT's contribution in stomach cancer. MALAT-1 expression appeared considerably greater in gastric cancer (GC) rats with remote miR-122-IGF-1R impact. MALAT-1 depletion inhibited cell cycle development, cell division and invasion, thus boosting death of GC cells. Likewise, miR-122-IGF-1R expression was linked to MALAT-1 deregulations in GC. Biological markers discovery based on biochemical data alongside detailed genome study might enhance prognosis, diagnosis and therapeutic compliance. This article summed up the most recent developments and techniques in GC biomarkers and may have applications for early detection, precise estimation of treatment strategies, and future perspectives according to molecular classification and profiling. In rats, GC was induced by 20-MCA, followed by DOX, Liposomal DOX, and PEGylated-Dox treatment. In addition to histopathological examinations, GC tumor biomarkers such as CEA, CA12–5, KRAS, AKT, PTEN, TP53, JAK-2, lnc- MALAT-1 and miR-122-IGF-1R were tracked. These findings reveal that MALAT-1 may be oncogenic in GC. Prominent MALAT-1 levels may assist as an indicator of metastasis in GC, and that miR-122-IGF-1R expression is associated via reduced MALAT-1 signaling. Finally, PEG-DOX may be an excellent option for GC therapy.

Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis

MALAT1, one of the few highly conserved nuclear long noncoding RNAs (lncRNAs), is abundantly expressed in normal tissues. Previously, targeted inactivation and genetic rescue experiments identified MALAT1 as a suppressor of breast cancer lung metastasis. On the other hand, Malat1-knockout mice are viable and develop normally. On a quest to discover the fundamental roles of MALAT1 in physiological and pathological processes, we find that this lncRNA is downregulated during osteoclastogenesis in humans and mice. Remarkably, Malat1 deficiency in mice promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic add-back of Malat1. Mechanistically, Malat1 binds to Tead3 protein, a macrophage-osteoclast–specific Tead family member, blocking Tead3 from binding and activating Nfatc1, a master regulator of osteoclastogenesis, which results in the inhibition of Nfatc1-mediated gene transcription and osteoclast differentiation. Notably, single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. Altogether, these findings identify Malat1 as a lncRNA that protects against osteoporosis and bone metastasis.

Possible role of lncRNAs in amelioration of Parkinson’s disease symptoms by transplantation of dopaminergic cells

Long non-coding RNAs (lncRNAs) are biomarkers for diagnosis and treatment of Parkinson’s disease (PD). Since dopaminergic cell transplantation is a clinical method to treat PD, this study investigated the effects of dopaminergic cell therapy on the expression of some lncRNAs and genes related to PD. In this study, Twenty-eight rats were randomly assigned to four experimental groups. The control group (Sal group) received saline injections. The Par group was a PD rat model with 6-hydroxydopamine (6-OHDA) injection in right striatum (ST). PD animals were transplanted by undifferentiated P19 stem cells (Par-E group), and P19-derived dopaminergic cells (Par-N group). Cell transplant effects were evaluated using behavioral tests (cylinder, open field, and rotarod tests), and histological methods (H&E and Nissl staining, and immunohistochemistry). Moreover, the expression of lncRNAs MALAT1, MEG3, and SNHG1, alongside specific neuronal (synaptophysin) and dopaminergic (tyrosine hydroxylase) markers was evaluated by qRT-PCR. Behavioral and histopathological examinations revealed that cell transplantation partially compensated dopaminergic cell degeneration in ST and substantia nigra (SN) of PD rats. The expression of MALAT1, SNHG1, and MEG3 was decreased in the ST of the Par group, while MEG3 and SNHG1 gene expression was increased in PBMC relative to the Sal group. In PBMC of the Par-N group, all three lncRNAs showed a reduction in their expression. Conversely, MALAT1 and SNHG1 expression was increased in ST tissue, while MEG3 gene expression was decreased compared to the Sal group. In conclusion, dopaminergic cell transplantation could change the lncRNAs expression. Furthermore, it partially improves symptoms in PD rats.

Expression of circulating long non-coding MALAT1 and GAS5 under metformin treatment in type 2 diabetic patients

The most prevalent metabolic disorder is type 2 diabetes. Long non-coding RNAs are one of the most effective factors in disease pathogenesis and are also promising therapeutic targets. GAS5 and MALAT1 are two lncRNAs that participate in glucose homeostasis. This study aims to compare the expression levels of lncRNA-GAS5 and lncRNA-MALAT1 in the PBMCs of T2DM patients with healthy individuals. A total of 60 diabetic patients and 60 healthy individuals were selected, including an equal number of males and females. The two groups of diabetic patients—those who had been taking metformin and those who hadn't—were further divided into two subgroups based on their BMI. Following PBMC RNA extraction, cDNA synthesis and the Real-Time qPCR method were used to assess the relative gene expression. Some diabetes risk factors, including elevated FBP, triglycerides, and WBC, and reduced AST enzyme, were observed in Iranian T2DM patients. Additionally, diabetic patients have lower levels of GAS5 and MALAT1 gene expression; nevertheless, T2DM patients' MALAT1 expression decreased in response to metformin treatment. However, increasing in BMI, can be elevated MALAT1 and GAS5 expression in normal individuals. Our study reveals that GAS5 and MALAT1 gene expression is reduced in T2DM patients, and their expression is also related to BMI. Furthermore, it is suggested to consider the effectiveness of new diabetes drugs based on the simulation of the expression pattern of pivotal long non-coding RNAs in the pathways involved in blood sugar regulation.

Platelet-rich plasma-derived extracellular vesicles inhibit NF-κB/NLRP3 pathway-mediated pyroptosis in intervertebral disc degeneration via the MALAT1/microRNA-217/SIRT1 axis

BackgroundIntervertebral disc degeneration (IDD) is a main contributor to lower back pain, and compression stress-induced apoptosis of nucleus pulposus (NP) cells and extracellular matrix (ECM) degradation has been implicated in the IDD progression. The functions of platelet-rich plasma (PRP)-derived extracellular vesicles (PRP-EVs) in regulating these biological processes remain unclear in IDD. Here, we aimed to investigate the key role of long noncoding RNA (lncRNA) MALAT1 incorporated in PRP-EVs in IDD. MethodsTert-butyl hydroperoxide (TBHP)-induced damage in NP cells was treated with PRP-EVs extracted from healthy volunteers, followed by MTT, EdU, TUNEL, and Western blot assays. IDD mice were also treated with PRP-EVs. Histomorphological and pathological changes were evaluated. The pyroptosis of cells and the degradation of ECM were detected by ELISA and immunohistochemistry. We screened the differentially expressed lncRNAs in NP cells after PRP-EVs treatment by microarray analysis. The downstream targets of MALAT1 in NP cells were predicted and validated by rescue experiments. FindingsTBHP induction reduced cell proliferation and exacerbated pyroptosis and ECM degradation, and PRP-EVs inhibited TBHP-induced cell damage. PRP-EVs-treated mice with IDD had reduced Thompson scores, increased NP tissue content, and restored ECM. PRP-EVs upregulated MALAT1 expression in vivo and in vitro, whereas MALAT1 downregulation exacerbated NP cell pyroptosis and ECM degradation. MALAT1 upregulated SIRT1 expression by downregulating microRNA (miR)-217 in NP cells. SIRT1 blocked the NF-κB/NLRP3 pathway-mediated pyroptosis, thereby alleviating IDD. InterpretationPRP-EVs deliver MALAT1 to regulate miR-217/SIRT1, thereby controlling NP cell pyroptosis in IDD.

Brucella abortus triggers the differential expression of immunomodulatory lncRNAs in infected murine macrophages.

The lncRNAs (long non-coding RNAs) are the most diverse group of non-coding RNAs and are involved in most biological processes including the immune response. While some of them have been recognized for their influence on the regulation of inflammatory activity, little is known in the context of infection by Brucella abortus, a pathogen that presents significant challenges due to its ability to manipulate and evade the host immune system. This study focuses on characterize the expression profile of LincRNA-cox2, Lethe, lincRNA-EPS, Malat1 and Gas5 during infection of macrophages by B. abortus. Using public raw RNA-seq datasets we constructed for a lncRNA expression profile in macrophages Brucella-infected. In addition, from public RNA-seq raw datasets of RAW264.7 cells infected with B. abortus we constructed a transcriptomic profile of lncRNAs in order to know the expression of the five immunomodulating lncRNAs studied here at 8 and 24 h post-infection. Finally, we performed in vitro infection assays in RAW264.7 cells and peritoneal macrophages to detect by qPCR changes in the expression of these lncRNAs at first 12 hours post infection, a key stage in the infection cycle where Brucella modulates the immune response to survive. Our results demonstrate that infection of macrophages with Brucella abortus, induces significant changes in the expression of LincRNA-Cox2, Lethe, LincRNA-EPS, Gas5, and Malat1. The change in the expression profile of these immunomodulatory lncRNAs in response to infection, suggest a potential involvement in the immune evasion strategy employed by Brucella to facilitate its intracellular survival.

MALAT1/miR-7-5p/TCF4 Axis Regulating Menstrual Blood Mesenchymal Stem Cells Improve Thin Endometrium Fertility by the Wnt Signaling Pathway.

Thin endometrium (TE) is a significant factor contributing to fertility challenges, and addressing this condition remains a central challenge in reproductive medicine. Menstrual blood-derived mesenchymal stem cells (MenSCs) play a crucial role in tissue repair and regeneration, including that of TE. The Wnt signaling pathway, which is highly conserved and prevalent in eukaryotes, is essential for cell proliferation, tissue development, and reproductive functions. MALAT1 is implicated in various transcriptional and molecular functions, including cell proliferation and metastasis. However, the combined effects of the Wnt signaling pathway and the long non-coding RNA (lncRNA) MALAT1 on the regulation of MenSCs' regenerative capabilities in tissue engineering have not yet been explored. To elucidate the regulatory mechanism of MALAT1 in TE, we analyzed its expression levels in normal endometrium and TE tissues, finding that low expression of MALAT1 was associated with poor clinical prognosis. In addition, we conducted both in vitro and in vivo functional assays to examine the role of the MALAT1/miR-7-5p/TCF4 axis in cell proliferation and migration. Techniques such as dual-luciferase reporter assay, fluorescent in situ hybridization, and immunoblot experiments were utilized to clarify the molecular mechanism. To corroborate these findings, we established a TE model and conducted pregnancy experiments, demonstrating a strong association between MALAT1 expression and endometrial fertility. In conclusion, our comprehensive study provides strong evidence supporting that lncRNA MALAT1 modulates TCF4 expression in the Wnt signaling pathway through interaction with miR-7-5p, thus enhancing MenSCs-mediated improvement of TE and improving fertility.

The Expression of TP53TG1, LINC00342, MALAT1, H19, and MEG3 Long Noncoding RNAs in Type 2 diabetes mellitus

Type 2 diabetes is a complex and multifactorial metabolic disorder. The frequency of type 2 diabetes has dramatically increased worldwide. Long noncoding RNAs play a regulatory role in pathological processes of type 2 diabetes. The aim of the study was to analyze TP53TG1, LINC00342, MALAT1, H19, and MEG3 lncRNAs in patients with type 2 diabetes and metabolic parameters, as well as the risk of diabetic retinopathy. Participants included 51 patients with diabetes and 70 healthy individuals. The expression of the TP53TG1 and LINC00342 genes was significantly decreased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was higher in diabetes patients. H19 gene expression was increased in the patients with diabetic retinopathy compared patients without retinopathy. TP53TG1, LINC00342, and MEG3 expression was decreased in patients with diabetic retinopathy and MALAT1 expression was increased. H19 is positively correlated with triglyceride levels; TP53TG1 and LINC00342 are positively correlated with HbA1c levels and fasting glucose levels. MALAT1 is negatively correlated with HDL levels and positively correlated with LDL levels. A decrease in the expression level of TP53TG1 and LINC00342 and an increase in the level of MALAT1 in diabetes, as well as an association with glycemic control, indicate the role of the studied noncoding RNAs in the development of type 2 diabetes mellitus and retinopathy and can be considered as candidates for early diagnosis of type 2 diabetes.

Effect of spermidine on long non-coding RNAs MALAT1 in a rotenone induced-rat model of Parkinson's disease.

Spermidine is a natural biologically active substance that has widespread influences on the body. This study aims to enhance our understanding of the potential effect of spermidine on long non-coding RNA MALAT1 and explore the underlying mechanism in the rotenone-induced rat model of Parkinson's disease. Rats were sacrificed after locomotor behavioral testing. Striatal tissues were used to assess the expression of MALAT1, oxidative stress markers, and autophagy markers. Our study found that treatment with spermidine for 2weeks during the induction of the model significantly improved behavioral assessment, dopamine levels, and attenuated the histopathological changes that occurred in PD in comparison to the non-treated group. Our preliminary study supports the protective effect of spermidine on the activation of autophagy and its antioxidant properties. Part of the antioxidant activity is due to the inhibition of MALAT1. However, MALAT1 does not correlate with the spermidine-induced autophagy pathway.

Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia.

Dysregulated expression of the long non-coding RNA MALAT1 has been implicated in the pathogenesis and progression of a variety of cancers, including hematological malignancies, but it has been poorly investigated in chronic lymphocytic leukemia (CLL). In this study, the expression of MALAT1 was measured using a quantitative reverse-transcriptase polymerase chain reaction in the peripheral blood mononuclear cells of 114 unselected, newly diagnosed CLL patients in order to analyze its association with clinical, laboratory, and molecular patients' characteristics at diagnosis, as well as its prognostic relevance. MALAT1 was found to be upregulated in CLL patients in comparison to healthy controls, and expression levels were not related to age, leukocyte, lymphocyte and platelet count, serum β2-microglobulin, and IGHV somatic hypermutational status. On the other hand, high MALAT1 expression was associated with several favorable prognostic markers (high hemoglobin, low serum lactate dehydrogenase, earlier clinical stages, CD38-negative status), but also with unfavorable cytogenetics. Furthermore, an association between high MALAT1 levels and longer time to first treatment and overall survival in IGHV-unmutated CLL subtype was observed. In summary, our results imply that high MALAT1 expression at diagnosis may be a predictor of better prognosis and point to MALAT1 expression profiling as a candidate biomarker potentially useful in clinical practice.