High Metastasis-associated Lung Adenocarcinoma Transcript 1 Expression Research Articles

Prognostic significance of MALAT1 in clear cell renal cell carcinoma based on TCGA and GEO.

Long noncoding RNAs metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) can regulate tumorigenesis and progression of various cancers. However, there is little known about the tumor biology and regulatory mechanism of MALAT1 in clear cell renal cell carcinoma (ccRCC). The objective of this study was to evaluate the prognostic value and potential functions of MALAT1 in ccRCC based on the cancer genome atlas. Through bioinformatics research, we analyzed the expression of MALAT1 in ccRCC, and the relationship with clinicopathological features, overall survival and infiltration of immune cells, and established the prognostic models. The results showed that MALAT1 was highly expressed in ccRCC tissues and predicted poor ccRCC patient outcome. The expression level of MALAT1 was significantly correlated with histologic grade, pathologic grade, T stage, M stage. ROC curve showed that MALAT1 had a good diagnostic accuracy, area under the curve of 0.752. The univariate and multivariate cox regression analysis showed that high MALAT1 expression was an independent prognostic factor for overall survival in the cancer genome atlas (hazard ratio = 2.271, 95% confidence interval: 1.435-3.593, P < .001). Gene set enrichment analysis revealed that MALAT1 expression was associated with the DNA methylation, epigenetic regulation of gene expression signaling pathway. In addition, the prognostic models were established to predict 1-, 3- and 5-year survival. This study showed that high expression of MALAT1 might be a potential diagnostic and prognostic biomarker.

Upregulation of Long Noncoding RNA MALAT1 in Colorectal Cancer Promotes Radioresistance and Aggressive Malignance.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a conserved transcript with 8000 nt, is highly associated with malignancy of numerous cancer types. However, the function of MALAT1 plays in regulating the response to radiotherapy in colorectal cancer (CRC) remains unclear. Thus, the object of this study is to investigate the functions of MALAT1 in CRC radioresistance. First, the expression of MALAT1 in colon adenocarcinoma (COAD) was analyzed through the Cancer Genome Atlas (TCGA) database. Then, we detected the expression level of MALAT1 in tumor tissues and CRC cell lines and analyzed the relevance of MALAT1 and clinicopathological parameters. In the end, the effect of silencing MALAT1 on the radiosensitivity of CRC cells was investigated, and its potential mechanism was preliminarily illustrated. The analysis of TCGA data showed that MALAT1 was closely related to the type of tumor, and high expression of MALAT1 was remarkably relevant to poor outcome. MALAT1 was highly expressed in CRC tissues and cell lines and related to tumor stages. Knockdown of MALAT1 could significantly suppress colony survival, proliferation, and migration and increase apoptosis, G2/M phase arrest, and formation of gamma-H2AX foci in HCT116, whether in combination with X-rays or not. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that the regulated proteins were principally enriched in the glycosaminoglycan degradation pathway after silencing MALAT1. Our results implied that MALAT1 was highly expressed in CRC and associated with tumor stage and prognosis. Silencing MALAT1 can increase HCT116 cell radiosensitivity, which may be potentially influenced by glycosaminoglycan degradation pathway.

Functional roles of long noncoding RNA MALAT1 in gynecologic cancers.

Gynecologic cancers are reproductive disorders characterized by pelvic pain and infertility. The identification of new predictive markers and therapeutic targets for the treatment of gynecologic cancers is urgently necessary. One of the recent successes in gynecologic cancers research is identifying the role of signaling pathways in the pathogenesis of the disease. Recent experiments showed long noncoding RNAs (lncRNA) can be novel therapeutic approaches for the diagnosis and treatment of gynecologic cancers. LncRNA are transcribed RNA molecules that play pivotal roles in multiple biological processes by regulating the different steps of gene expression. Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) is a well-known lncRNA that plays functional roles in gene expression, RNA processing, and epigenetic regulation. High expression of MALAT1 is closely related to numerous human diseases. It is generally believed that MALAT1 expression is associated with cancer cell growth, autophagy, invasion, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) could contribute to the pathogenesis of gynecologic cancers. In this review, we will summarize functional roles of MALAT1 in the most common gynecologic cancers, including endometrium, breast, ovary, and cervix.

Does MALAT1 (NEAT2) Predict the Prognosis of Sepsis in Pediatric Patients?

Background: Sepsis is one of the major causes of disability and death in the pediatric population globally. Although metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be associated with the survival of adult patients with sepsis, its prognostic value in children has not been identified. Objectives: The present study aimed to evaluate the role of MALAT1 in the prognosis of severe sepsis in children. Methods: A total of 60 children with severe sepsis were included in this research. Serum level of MALAT1 was assessed at baseline, and the survival data were recorded during a follow-up of 28 days. These participants were categorized into high or low MALAT1 groups based on the median value. Multivariate Cox regression was performed to explore the association of MALAT1 level with the survival of pediatric patients with sepsis after controlling for potential confounding factors. Results: The 28-day mortality rate of severe sepsis was 35%. The expression of MALAT1 in the non-survivors was significantly higher than in the survived patients (P &lt; 0.01). The multivariate Cox proportional hazards model, showed that a higher MALAT1 expression was associated with a higher risk of mortality in patients with severe sepsis (HR = 6.70; 95% CI: 1.65 - 27.2; P &lt; 0.01). Conclusions: According to our results, MALAT1 might be a promising marker for predicting the prognosis of severe pediatric sepsis.

Diabetes Mellitus-Mediated MALAT1 Expression Induces Glioblastoma Aggressiveness.

To describe the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in glioblastoma (GB) progression in patients concurrently diagnosed with diabetes mellitus (DM). Formalin-fixed paraffin-embedded (FFPE) tumor samples of 47 patients diagnosed with GB only and 13 patients diagnosed with GB and DM (GB-DM) were enrolled in this study. Data for p53 and Ki67 immunohistochemical staining of the tumors and blood HbA1c levels of patients with DM were retrospectively collected. MALAT1 expression was assessed using quantitative real-time polymerase chain reaction. The coexistence of GB and DM induced the nuclear expression of p53 and Ki67 compared with GB only. MALAT1 expression was higher in GB-DM tumors than in GB only tumors. The expression of MALAT1 and HbA1c levels were positively correlated. Additionally, MALAT1 was positively correlated with tumoral p53 and Ki67. The disease-free survival of patients with GB-DM with high MALAT1 expression was shorter than that of those diagnosed with GB only and with a lower MALAT1 expression. Our findings suggest that one of the mechanisms of the facilitating effect of DM on GB tumor aggressiveness is via MALAT1 expression.

Preclinical evaluation of [68Ga]Ga-MALAT-1-antisense oligonucleotides for specific PET imaging of MALAT-1 expressing tumours

The present study was to explore the feasibility of developing positron molecular probes for the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), to evaluate the distribution and pharmacokinetics, and to explore whether the probe can be used for the imaging of malignant tumours with high MALAT-1 expression in vivo. [68Ga]Ga labelling of MALAT-1 antisense oligonucleotides ([68Ga]Ga-MALAT-1-ASO) was synthesized by the conjugation of MALAT-1-NOTA-ASO and [68Ga] Ga3+. The radiochemical purity was shown by radio-HPLC. Pharmacokinetic studies and cellular uptake studies were performed. The biodistribution and metabolism of [68Ga] Ga-MALAT-1-ASO in normal ICR and MHCC-LM3 xenograft-bearing nude mice were studied in vitro and in vivo. [68Ga]Ga-MALAT-1-ASO was obtained in 98% radiochemical yield from a 10-min synthesis with 100 ± 50 MBq/nmol specific activity and >99% radiochemical purity. The Log D was -2.53 ± 0.19. The tracer displayed excellent stability in vitro. 68Ga-MALAT-1 ASO showed satisfactory binding ability to MHCC-LM3 cells; the biodistribution of [68Ga]Ga-MALAT-1-ASO in MHCC-LM3 tumour-bearing mice demonstrated specific uptake of the radiotracer (3.04 ± 0.11%ID/g). Micro-PET images of the MHCC-LM3 cell xenograft mouse model provided further evidence to support the hypothesis that [68Ga]Ga-MALAT-1-ASO can target tumours in vivo. We conclude that [68Ga]Ga labelling of MALAT-1 ASO is a convenient approach. The high accumulation of [68Ga]Ga-MALAT-1-ASO for tumours expressing MALAT-1 suggests that this radio compound may be used as a potential positron molecular probe. Molecular structure optimization studies need to be more in-depth to further reduce its background uptake and enhance tumour targeting.

High-Dose Vitamin C Tends to Kill Colorectal Cancer with High MALAT1 Expression.

Background Vitamin C (Vc) deficiency is frequently observed in cancer sites and has been proposed to have an antitumor effect. However, the mechanism of Vc's killing effect is not clear. Besides, epigenetic alterations exhibit significant effects on colorectal cancer (CRC). This study aimed to explore the mechanism of Vc's killing effect and its association to epigenetic alterations in CRC. Methods Cell morphology, apoptosis, proliferation, and cycle were assayed to test Vc's suppressive function in CRC cell lines. Xenograft and peritoneal implantation metastasis models were performed to evaluate the high-dose Vc's inhibitory effect on tumor growth and metastasis. Immunohistochemistry was used to measure CD31 expression in solid tumors. A literature summary was applied for screening differently expressed long noncoding RNAs (lncRNAs) in CRC tissues and was closely associated with CRC progression. The qPCR was used to detect the expression of these lncRNAs. The association between Vc and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was evaluated in MALAT1-transfected CRC cells and a xenograft model. Results Vc was confirmed to function in proliferation suppression, apoptosis induction, and S phase arresting in CRC cell lines. High-dose Vc, but not physiologically low-dose Vc, was identified as a suppressive function on tumor growth in xenograft models and an inhibitory effect on implantation metastasis in peritoneal implantation metastasis mice. Furthermore, a consistent downregulation of MALAT1 induced by Vc was verified among CRC cell lines and tumor tissues from both mouse models. Finally, experiments on MALAT1-knockdown CRC cells and its xenograft model suggested that Vc had a tendency in killing CRC with high MALAT1 expression. Conclusions Our findings demonstrate that high-dose Vc has more efficiency in suppressing CRC with higher MALAT1 expression. It gives high-dose Vc the possibility of a better curative effect on CRC with overexpressed MALAT1. Further clinical studies are still needed.

&lt;p&gt;LncRNA MALAT1 Promotes Survival of Epithelial Ovarian Cancer Cells by Downregulating miR-145-5p&lt;/p&gt;

PurposeThis paper was aimed at investigating the regulatory mechanism of long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) in epithelial ovarian cancer (EOC).Materials and MethodsMALAT1 and miR-145-5p expression in the tissues, serum, and EOC cell lines (TOV-112D, TOV-21G) of patients with EOC were detected. The two genes were transfected into the cells via upregulating or downregulating their expression. Levels of apoptosis-related proteins (Caspase-3, Bax, Bcl-2) were analyzed. Mechanisms of cell proliferation, invasion, and apoptosis were studied.ResultsMALAT1 was high expressed in EOC tissues, while miR-145-5p was poorly expressed in them. The areas under the curves (AUCs) of the two genes for diagnosing EOC were greater than 0.850, and the two had a significantly negative correlation. According to multivariate Cox regression analysis, high MALAT1 expression, tumor size, degree of differentiation, case staging, and lymph node metastasis were the independent risk factors affecting prognosis. The 5-year overall survival rate (OSR) of patients with low MALAT1 expression was remarkably higher than that of those with high expression. Overexpressing miR-145-5p and silencing MALAT1 could inhibit EOC cells from proliferating and invading, increase their apoptotic rate, and improve levels of the apoptosis-related proteins. After co-transfection with MALAT1-inhibitor + miR-145-5p-inhibitor, the proliferation and invasion of TOV-112D and TOV-21G cells were inhibited and the apoptotic rate rose more obviously. Inhibiting MALAT1 could increase miR-145-5p expression, thus inhibiting EOC cells from proliferating and invading and thereby increasing their apoptotic rate.ConclusionMALAT1 promotes EOC cells’ survival by downregulating miR-145-5p so it may become a new direction for EOC diagnosis and gene therapy.

Exercise-mediated downregulation of MALAT1 expression and implications in primary and secondary cancer prevention

Long non-coding RNAs (lncRNAs) play critical roles in various biological functions and disease processes including cancer. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was initially identified as a lncRNA with elevated expression in primary human non-small cell lung tumors with high propensity to metastasize, and subsequently shown to be highly expressed in numerous other human cancers including breast, ovarian, prostate, cervical, endometrial, gastric, pancreatic, sarcoma, colorectal, bladder, brain, multiple myeloma, and lymphoma.MALAT1 is deeply involved in several physiological processes, including alternative splicing, epigenetic modification of gene expression, cellular senescence, healthy aging, and redox homeostasis.The aim of this work was to investigate the modulation exerted by a single bout of endurance exercise on the level of MALAT1 expression in peripheral blood mononuclear cells (PBMCs) from healthy male donors displaying different training status and redox homeostasis features. Our findings show that MALAT1 is downregulated after acute endurance exercise in subjects whose fitness level guarantee a high expression of SOD1 and SOD2 antioxidant genes and low levels of endogenous oxidative damage. In vitro protocols in Jurkat lymphoblastoid cells exposed to pro-oxidant environment confirmed the link between MALAT1 expression and antioxidant gene modulation, documenting p53 phosphorylation and its recruitment to MALAT1 promoter. Remarkably, analyses of Microarray-Based Gene Expression Profiling revealed high MALAT1 expression in leukemia patients in comparison to healthy control and a significant negative correlation between MALAT1 and SOD1 expression.Collectively our results highlight the beneficial effect of a physically active lifestyle in counteracting aberrant cancer-related gene expression programs by improving the redox buffering capacity.

Silencing of long non-coding RNA MALAT1 suppresses inflammation in septic mice: role of microRNA-23a in the down-regulation of MCEMP1 expression.

Sepsis is a life-threatening disease without ideal biomarkers. Some long non-coding RNAs (lncRNAs) are found to be implicated in sepsis. Thus, we investigated the effects of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on inflammation in septic mice and the potential mechanisms of the MALAT1/microRNA-23a (miR-23a)/MCEMP1 axis. The sepsis mice model was generated by cecal ligation and puncture (CLP). Then the expressions of lncRNA MALAT1, mast cell-expressed membrane protein 1 (MCEMP1), and miR-23a in septic mice were determined. The interaction between lncRNA MALAT1, miR-23a and MCEMP1 was confirmed. Loss- and gain-of-function approaches were used to verify the roles of the lncRNA MALAT1, miR-23a, and MCEMP1 in inflammation, cell proliferation and apoptosis in septic mice. The myeloperoxidase (MPO) activity and the expression of interleukin 6 (IL-6), IL-1β, IL-10, and tumor necrosis factor-α (TNF-α) were detected. High expression of the lncRNA MALAT1 and MCEMP1, as well as low expression of miR-23a, was observed in septic mice. LncRNA MALAT1 competitively bound to miR-23a, and miR-23a targeted MCEMP1. Moreover, the down-regulation of lncRNA MALAT1 repressed the expression of MPO, IL-6, IL-10, TNF-α, and IL-1β. Silencing of lncRNA MALAT1 or overexpression of miR-23a reduced inflammation, inhibited cell proliferation, and promoted cell apoptosis in septic mice. Taken together, MALAT1 promotes the inflammation in septic mice by binding to miR-23a to up-regulate MCEMP1. Therefore, silencing of lncRNA MALAT1 might provide a novel therapeutic target for sepsis.

LncRNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promotes Proliferation and Invasion of Non-Small Cell Lung Cancer Cells via Down-Regulating miR-202 Expression.

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. ConclusionThis 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.

LncRNA MALAT1 Accelerates Skeletal Muscle Cell Apoptosis and Inflammatory Response in Sepsis by Decreasing BRCA1 Expression by Recruiting EZH2

Sepsis is a serious and elusive syndrome caused by infection, which is accompanied by a high mortality worldwide. Recent evidence has documented the regulatory role of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) during the inflammatory process, the effects of which in the development of sepsis have become the focus of the current study. An in vivo mouse model and in vitro cell model of sepsis induced by lipopolysaccharide (LPS) were developed. High expression of lncRNA MALAT1 along with low expression of breast cancer susceptibility gene 1 (BRCA1) were identified in septic mice and human skeletal muscle cells of sepsis. Then, lncRNA MALAT1 expression was altered in vivo and in vitro to examine serum levels of inflammatory factors, as well as skeletal muscle cell apoptosis. lncRNA MALAT1 was noted to regulate the expression and export from the nucleus of BRCA1 by recruiting zeste homolog 2 (EZH2) in skeletal muscle cells of sepsis. Silencing lncRNA MALAT1 resulted in reduced serum levels of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), neutrophil migration, skeletal muscle cell apoptosis, and AKT-1 phosphorylation. Taken together, lncRNA MALAT1 interacting with EZH2 stimulated AKT-1 phosphorylation and decreased BRCA1 expression, consequently aggravating the progression of sepsis, highlighting a promising therapeutic option for sepsis.

Long noncoding RNA MALAT1 may be a prognostic biomarker in IDH1/2 wild-type primary glioblastomas.

Primary glioblastoma (GB) is the most aggressive type of brain tumors. While mutations in isocitrate dehydrogenase (IDH) genes are frequent in secondary GBs and correlate with a better prognosis, most primary GBs are IDH wild-type. Recent studies have shown that the long noncoding RNA metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is associated with aggressive tumor phenotypes in different cancers. Our aim was to clarify the prognostic significance of MALAT1 in IDH1/2 wild-type primary GB tumors. We analyzed IDH1/2 mutation status in 75 patients with primary GB by DNA sequencing. The expression of MALAT1 was detected in the 75 primary GB tissues and 5 normal brain tissues using reverse transcription quantitative PCR (RT-qPCR). The associations between MALAT1 expression, IDH1/2 mutation status, and clinicopathological variables of patients were determined. IDH1 (R132H) mutation was observed in 5/75 primary GBs. IDH2 (R172H) mutation was not detected in any of our cases. MALAT1 expression was significantly upregulated in primary GB vs. normal brain tissues (p = 0.025). Increased MALAT1 expression in IDH1/2 wild-type primary GBs correlated with patient age and tumor localization (p = 0.032 and p = 0.025, respectively). A multivariate analysis showed that high MALAT1 expression was an unfavorable prognostic factor for overall survival (p = 0.034) in IDH1/2 wild-type primary GBs. High MALAT1 expression may have a prognostic role in primary GBs independent of IDH mutations.

High Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Expression Promotes Proliferation, Migration, and Invasion of Non-Small Cell Lung Cancer via ERK/Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway.

BackgroundIn present study, we explored the function of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) gene in the development of non-small cell lung cancer (NSCLC).Material/MethodsqRT-PCR was used to detect the MALAT1 mRNA expression level in cancer tissues and adjacent normal tissues of 115 NSCLC patients and in cell lines. MALAT1-mimic, MALAT1-inhibitor, and corresponding negative controls (NC) were utilized to transfect the H460 cells. Proliferation, migration, and invasion of H460 cells were evaluated by MTT method and Transwell assay. Expression levels of proteins in the ERK/MAPK signaling pathway were assessed by Western blot analysis.ResultsMALAT1 mRNA was upregulated in NSCLC tissues and cell lines compared to that in adjacent tissues and normal human bronchial cell line (BEAS-2B), respectively. Overexpression of MALAT1 significantly strengthened the proliferation, migration, and invasion ability of H460 cells. In comparison with the NC group, expression levels of CXCL5 and p-JNK proteins were elevated, while p-MAPK and p-ERK proteins were decreased in the MALAT1-mimic group. MALAT1 targets the 3′-untranslated region (UTR) fragment of the CXCL5 gene and inhibits its translation. Disturbance of the CXCL5 gene can reduce the protein expression of MAPK, p-MEK1/2, p-ERK1/2, and p-JNK, and inhibit the proliferation, migration, and invasion of MALAT1-mimic cells.ConclusionsHigh MALAT1 expression promotes the proliferation, migration, and invasion of non-small cell lung cancer via the ERK/MAPK signaling pathway.

Long Non-Coding RNA MALAT1 Accelerates Skeletal Muscle Cell Apoptosis and Inflammatory Response in Sepsis Through Decreasing BRCA1 Expression by Recruiting EZH2

Background: Sepsis is a serious and elusive syndrome caused by infection, which is accompanied by a high rate of mortality worldwide. Studies have speculated the role of long non-coding RNAs (lncRNAs) in sepsis. However, the potential role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in sepsis is largely unknown. Thus, the present study intended to investigate the possible role of MALAT1 in relation to the development of sepsis and to explore the underlying mechanism. Methods: In vivo mouse model and in vitro cell model of sepsis induced by lipopolysaccharide (LPS) were constructed. Then in order to evaluate the effect of MALAT1 on the progression of sepsis, the expression of MALAT1 was silenced in sepsis mice, followed by the measurement of number of neutrophils in peripheral blood, serum levels of inflammatory factors, as well as skeletal muscle cell apoptosis. Furthermore, interactions among MALAT1, EZH2 and BRCA1 and the regulatory role of MALAT1/EZH2 on sepsis were determined in skeletal muscles cells of sepsis. Results: High expression of MALAT1 along with low expression of BRCA1 was detected in sepsis. MALAT1 was observed to regulate the expression and nucleation of BRCA1. Silencing MALAT1 resulted in reduced serum levels of IL-6, IL-8 and TNF-α, neutrophil migration, skeletal muscle cell apoptosis, number of EZH2 positive cells, extent of AKT-1 phosphorylation along with stimulated BRCA1 expression. Furthermore, MALAT1 regulated the expression and localization of BRCA1 by recruiting EZH2. Conclusion: Taken together, the key observations of the study provide evidence that MALAT1 interacting with EZH2 stimulated AKT-1 phosphorylation and decreased BRCA1 expression, consequently aggravating the progression of sepsis, highlighting a promising therapeutic option for sepsis. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81772128). Declaration of Interests: The authors have declared that no competing interests exist. Ethics Approval Statement: All animal experiment protocols were approved by the Animal Care Committee of The First Affiliated Hospital of Southwest Medical University and were in compliance with the guidelines established by the Guide for the Care and Use of Laboratory Animals.

MALAT1 and BACH1 are prognostic biomarkers for triple-negative breast cancer.

The purpose of this study was to investigate the potential correlation between metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the transcription factor BTB and CNC homology 1 (BACH1) and their clinicopathological significance in triple-negative breast cancer (TNBC). MALAT1 and BACH1 were detected by immunohistochemistry using TNBC tissue microarrays of 240 patients. The association between MALAT1 and BACH1 expression levels was statistically analyzed. Moreover, the prognostic roles as well as clinical and pathological significance of MALAT1 and BACH1 expression in TNBC were determined. Two-tailed Pearson correlation was used to examine the correlation of BACH1 and MALA1 expression. Comparisons of clinicopathological variables between different BACH1 and MALA1 expression groups were performed using χ2 tests. Overall survival (OS) and disease-free survival (DFS) curves were plotted with the Kaplan-Meier method and the differences in OS and DFS between three groups were compared by the log-rank test. Multiple comparisons were performed using χ2 tests for subsequent individual group comparisons. MALAT1 and BACH1 expression was significantly correlated with tumor-node-metastasis stage, distant metastasis, pathological stage, and survival outcomes of patients. Patients with high MALAT1 and BACH1 expression exhibited shorter overall survival and disease-free survival. These findings provide further insight into the expression pattern of MALAT1 and BACH1 in TNBC and suggest them as prognostic biomarkers for TNBC.

LncRNA MALAT1 promotes migration and invasion of non-small-cell lung cancer by targeting miR-206 and activating Akt/mTOR signaling.

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) functions as a crucial regulator of metastasis in lung cancer. The aim of this study is to unravel the underlying mechanisms of lncRNA MALAT1 in non-small-cell lung cancer (NSCLC). A cohort of 36 NSCLC tumor tissues and adjacent normal tissues was collected postoperatively from patients with NSCLC. qRT-PCR was performed to detect the expression of MALAT1 in both NSCLC tissues and cell lines. Cell migration and invasion were monitored by wound healing assay and transwell invasion assay. Western blot was used to detect the expression levels of epithelial-mesenchymal transition proteins and Akt/mTOR key components after treatment. Dual luciferase reporter assay coupled with qRT-PCR was used to verify the direct interaction between MALAT1 and miR-206. MALAT1 was significantly up-regulated in both NSCLC tissues and cell lines. High expression of MALAT1 correlated positively with tumor size and lymphatic metastasis in NSCLC, whereas no correlation was found between MALAT1 expression and sex, age, clinical stage, and histological grade. We also showed that MALAT1 promoted epithelial-mesenchymal transition, cell migration, and invasion by activating Akt/mTOR signaling in A549 and H1299 cells. miR-206 was a direct downstream target of MALAT1 in NSCLC. MALAT1 promoted cell migration and invasion by sponging miR-206 in NSCLC cells. In addition, miR-206 inhibited MALAT1-mediated activation of Akt/mTOR signaling in A549 and H1299 cells. lncRNA MALAT1 promotes migration and invasion of NSCLC by targeting miR-206 and activating Akt/mTOR signaling.

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a prognostic marker for the metastasis of early-stage non-small cell lung cancer (NSCLCs). We studied MALAT1 expression in breast cancer in relation to disease features and patient survival. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure MALAT1 expression in tumor samples of 509 breast cancer patients. Hazards ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between MALAT1 expression and breast cancer survival using the Cox proportional hazards regression model, and the analysis was adjusted for age at surgery, tumor grade, disease stage, and hormone receptor status. Meta-analysis of multiple microarray datasets from online databases and our own study was performed to evaluate the association of MALAT1 with breast cancer survival. Patients with low-grade or ER-positive tumors had higher expression of MALAT1 compared to those with high-grade (p = 0.013) or ER-negative (p = 0.0002) tumors. Patients with PR-positive tumors also had higher MALAT1 expression than those with PR-negative tumors (p < 0.0001). In patients with positive hormone receptors or low tumor grade, tumors with high MALAT1 expression were more likely to recur. Survival analysis showed that patients with high expression of MALAT1 had a twofold increase in risk of relapse (p = 0.0083) compared to those with low expression. This association remained significant after adjustment for age at surgery, disease stage, tumor grade, and hormone receptor status. Meta-analysis showed that high MALAT1 expression was associated with poor relapse-free survival in patients with hormone receptor-positive tumors (HR 1.44, 95% CI 1.08-1.92). High expression of lncRNA MALAT1 is associated with breast cancer relapse and may play a role in tumor progression.

Expression of metastasis-associated lung adenocarcinoma transcript 1 long non-coding RNA in vitro and in patients with non-small cell lung cancer.

The present study aimed to investigate the association between the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNA (lncRNA) and the recurrence of non-small cell lung cancer (NSCLC) and to elucidate the potential mechanisms of MALAT1 in vitro. Between 1 June 1, 2010 and December 30, 2016, NSCLC tumor tissues and adjacent non-cancerous tissues were obtained from 120 patients with NSCLC, who had undergone surgical resection at Taizhou Hospital of Wenzhou Medical University (Linhai, China). The total RNA of tissues and cells were extracted and the expression of MALAT1 was determined using a wound healing assay and reverse transcription quantitative polymerase chain reaction. In addition, MALAT1 expression in A549 cells was silenced using small interfering RNA. The proliferation, migration and invasion of cells were then assessed using a CellTiter 96 kit and Transwell assays. MALAT1 expression was significantly increased in NSCLC samples compared with expression in adjacent non-cancerous tissues. Furthermore, the expression of MALAT1 in patients with NSCLC that exhibited recurrence was markedly higher than in those that did not. The results of the present study also demonstrated significant associations between high expression of MALAT1 and female sex, Tumor-Node-Metastasis advanced stage, vessel invasion, pathological differentiation and recurrence of patients with NSCLC. The proliferative, migratory and invasive abilities of MALAT1-silenced A549 cells were significantly decreased compared with those of control cells. MALAT1 expression was significantly increased in NSCLC tissues and was revealed to serve a role in the progression of NSCLC.

Chronic oxymatrine treatment induces resistance and epithelial‑mesenchymal transition through targeting the long non-coding RNA MALAT1 in colorectal cancer cells.

A major reason for colorectal cancer (CRC) chemoresistance is the enhanced migration and invasion of cancer cells, such as the cell acquisition of epithelial-mesenchymal transition (EMT). Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been considered as a pro-oncogene in multiple cancers. However, the precise functional mechanism of lncRNA MALAT1 in chemoresistance and EMT is not well known. In the present study, we focused on the effect of oxymatrine on CRC cells and further investigated the role of MALAT1 in oxymatrine-induced resistance and EMT process. The human CRC cell line HT29 was exposed to increasing doses of oxymatrine to establish stable cell lines resistant to oxymatrine. The established HT29 oxymatrine resistant cells showed an EMT phenotype including specific morphologic changes, enhanced migratory and invasive capacity, and downregulation of E-cadherin protein expression. Subsequently, high-throughput HiSeq sequencing and RT-qPCR showed that lncRNA MALAT1 was significantly upregulated in the oxymatrine resistant cells (P<0.01), while knockdown of MALAT1 partially reversed the EMT phenotype in HT29 resistant cells. Furthermore, oxymatrine treatment suppressed the migration and invasion ability of CRC cells, however, this effect was significantly reversed by overexpression of MALAT1. Finally, we investigated the clinical role of MALAT1 and found that high lncRNA MALAT1 expression level is associated with poor prognosis in CRC patients receiving oxymatrine treatment (P<0.01). In conclusion, we demonstrate that lncRNA MALAT1 is a stimulator for oxymatrine resistance in CRC and it may provide therapeutic and prognostic information for CRC patients.