Air pollution, genetic factors, and chronic rhinosinusitis: A prospective study in the UK Biobank.

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent upper respiratory condition that manifests in two primary subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While previous studies indicate a correlation between air pollution and CRS, the role of genetic predisposition in this relationship remains largely unexplored. We hypothesized that higher air pollution exposure would lead to the development of CRS, and that genetic susceptibility might modify this association. METHODS: This cohort study involving 367,298 adult participants from the UK Biobank, followed from March 2006 to October 2021. Air pollution metrics were estimated at residential locations using land-use regression models. Cox proportional hazard models were employed to explore the associations between air pollution exposure and CRS, CRSwNP, and CRSsNP. A polygenic risk score (PRS) was constructed to evaluate the joint effect of air pollution and genetic predisposition on the development of CRS. RESULTS: We found that the risk of CRS increased under long-term exposure to PM2.5 [the hazard ratios (HRs) with 95 % CIs: 1.59 (1.26-2.01)], PM10 [1.64 (1.26-2.12)], NO2 [1.11 (1.04-1.17)], and NOx [1.18 (1.12-1.25)], respectively. These effects were more pronounced among participants with CRSwNP, although the differences were not statistically significant. Additionally, we found that the risks for CRS and CRSwNP increased in a graded manner among participants with higher PRS or higher exposure to PM2.5, PM10, or NOx concentrations. However, no multiplicative or additive interactions were observed. CONCLUSIONS: Long-term exposure to air pollution increases the risk of CRS, particularly CRSwNP underscoring the need to prioritize clean air initiatives and environmental regulations.

Astragaloside IV alleviates macrophage senescence and d-galactose-induced bone loss in mice through STING/NF-κB pathway.

BACKGROUND: Senile osteoporosis (SOP) is an age-related metabolic bone disease that currently lacks specific therapeutic interventions. Thus, this study aimed to investigate the effect of Astragaloside IV (AS-IV) on macrophage senescence, bone marrow mesenchymal stem cell (BMSC) osteogenesis, and SOP progression. METHODS: A senescent macrophage model was established and treated with varying concentrations of AS-IV. Cell activity was measured using the CCK8 assay. The senescence levels of macrophages were evaluated through ß-galactosidase staining, PCR, and immunofluorescence. Macrophage mitochondrial function was assessed using ROS and JC-1 staining. Macrophage polarization was evaluated through PCR, Western blot, and immunofluorescence. The inhibitory effects of AS-IV on macrophage senescence were investigated using Western blot analysis. Furthermore, the effects of macrophage conditioned medium (CM) on BMSCs osteogenic were detected using ALP, alizarin red, and PCR. RESULTS: AS-IV inhibited macrophage senescence and M1 polarization, alleviated mitochondrial dysfunction, and promoted M2 polarization. Mechanistically, it suppressed the STING/NF-κB pathway in H2O2-activated macrophages. Conversely, the STING agonist c-di-GMP reversed the effects of AS-IV on macrophage senescence. Additionally, AS-IV-induced macrophage CM promoted BMSC osteogenic differentiation. In vivo, AS-IV treatment ameliorated aberrant bone microstructure and bone mass loss in the SOP mouse model, inhibited macrophage senescence, and promoted M2 polarization. CONCLUSIONS: By modulating the STING/NF-κB signaling pathway, AS-IV potentially inhibited macrophage senescence and stimulated osteogenic differentiation of BMSCs, thus exerting an anti-osteoporotic effect. Consequently, AS-IV may serve as an effective therapeutic candidate for the treatment of osteoporosis.

The incidence of asthma attributable to temperature variability: An ecological study based on 1990-2019 GBD data.

BACKGROUND: Asthma, the second leading cause of death from chronic respiratory diseases, is associated with climate change, especially temperature changes. It is currently unclear about the relationship between long-term temperature variability and the incidence of asthma on a global scale. METHODS: We used asthma incidence, demographic and socioeconomic data from the Global Burden of Disease (GBD) Results Database, and environmental and geographical statistics from TerraClimate between 1990 and 2019 to determine the association between maximum temperature variability and asthma incidence. We also predicted the incidence of heat-related asthma in the future (2020-2100) under four shared socioeconomic pathways (SSPs: 126, 245, 370, and 585). RESULTS: Between 1990 and 2019, the global median incidence of asthma was 402.0 per 100,000 with a higher incidence (median: 1380.3 per 100,000) in children under 10 years old. We found that every 1 °C increase in maximum temperature variability increased the risk of asthma globally by 5.0 %, and the effect was robust for individuals living in high-latitude areas or aged from 50 to 70 years. By 2100, the average incidence of asthma is estimated to be reduced by 95.55 %, 79.32 %, and 40.02 % under the SSP126, SSP245, and SSP370 scenarios, respectively, compared to the SSP585 at latitudes >60°. CONCLUSION: Our study provides evidence that maximum temperature variability is associated with asthma incidence. These findings suggest that implementing stricter mitigation and adaptation strategies may be importment in reducing asthma cases caused by climate change.

Association between ambient temperature and chronic rhinosinusitis.

BACKGROUND: Chronic exposure to particulate matter air pollution (PM2.5 ) is associated with chronic rhinosinusitis (CRS). Elevated ambient temperature may increase PM2.5 levels and thereby exacerbate sinonasal symptoms. This study investigates the association between high ambient temperature and the risk of CRS diagnosis. METHODS: Patients with CRS were diagnosed at Johns Hopkins hospitals from May to October 2013-2022, and controls were matched patients without CRS meanwhile. A total of 4752 patients (2376 cases and 2376 controls) were identified with a mean (SD) age of 51.8 (16.8) years. The effect of maximum ambient temperature on symptoms was estimated with a distributed lag nonlinear model (DLNM). Extreme heat was defined as 35.0°C (95th percentile of the maximum temperature distribution). Conditional logistic regression models estimated the association between extreme heat and the risk of CRS diagnosis. RESULTS: Exposure to extreme heat was associated with increased odds of exacerbation of CRS symptoms (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.03-1.19). The cumulative effect of extreme heat during 0-21 lag days was significant (OR 2.37, 95% CI 1.60-3.50) compared with the minimum morbidity temperature (MMT) at 25.3°C. Associations were more pronounced among young and middle-aged patients and patients with abnormal weight. CONCLUSIONS: We found that short-term exposure to high ambient temperature is associated with increased CRS diagnosis, suggesting a cascading effect of meteorological phenomena. These results highlight climate change's potentially deleterious health effects on upper airway diseases, which could have a significant public health impact.

Effects of different doses of lithium on the central nervous system in the rat valproic acid model of autism.

Epidemiological studies have shown that low doses of lithium in the environment can have beneficial effects on mental health. Autism spectrum disorder, a neurodevelopmental disorder in which patients exhibit abnormal behaviors, pharmacological interventions usually relied on a range of psychotropic medications. However, such medications often produce severe side effects or are ineffective in symptoms. Finding alternative ways to improve abnormal behaviors in individuals with autism are warranted, in which case lithium may be a relatively safe and effective medication. Lithium salt therapy is used to treat a variety of neuropsychiatric disorders and has neuroprotective effects. In this study, we investigated the effects of different doses of lithium on neurobehavioural disorders using the rat model of autism established by valproic acid (VPA) injection. Lithium was observed to have an ameliorative effect on the social cognitive, social memory and anxiety levels in the rat model of autism. Immunofluorescence staining showed that subchronic LiCl administration (1.0 mmol/kg) significantly reduced the number of Iba-1 positive cells in the CA1 region of the hippocampus in VPA group and brought it close to the levels of control group. Significantly lower levels of the pro-inflammatory marker IL-6 were observed in the hippocampus and serum after lithium treatment. In addition, the lithium treatment increased the levels of H3K9 acetylation in the hippocampus of VPA-exposed rats. The results showed a defensive effect of environment-related lithium exposure doses on neurobehavioural deficits in the rat valproic acid model of autism, suggesting that it may be a potential drug for the treatment of autism.

Exposure to a real traffic environment impairs brain cognition in aged mice.

Traffic-related air pollution (TRAP) has been a common public health problem, which is associated with central nervous system dysfunction according to large-scale epidemiological studies. Current studies are mostly limited to artificial laboratory exposure environments and specific genetic mechanisms remain unclear. Therefore, we chose a real-world transportation environment to expose aged mice, transporting them from the laboratory to a 1-m-high dry platform inside the campus and tunnel, and the mice were exposed daily from 7 a.m. to 7 p.m. for 2, 4 and 12 weeks respectively. Compared with the control group (in campus), the memory function of mice in the experimental group (in tunnel) was significantly impaired in the Morris water maze test. TRAP exposure increased the number of activated microglia in the hippocampal DG, CA1, CA3 regions and dorsolateral prefrontal cortex (dPFC). And neuroinflammation and oxidative stress levels were up-regulated in both hippocampus and dPFC of aged mice. By screening the risk genes of Alzheimer's disease, we found the mRNA and protein levels of ABCA7 were down-regulated and those of PYK2 were up-regulated. The DNA methylation ratios increased in four CpG sites of abca7 promoter region and decreased in one CpG site of pyk2 promoter region, which were consistent with the altered expression of ABCA7 and PYK2. In conclusion, exposure to the real traffic environment impaired memory function and enhanced neuroinflammation and oxidative stress responses, which could be relevant to the altered expression and DNA methylation levels of ABCA7 and PYK2. Our work provides a new and promising understanding of the pathological mechanisms of cognitive impairment caused by traffic-related air pollution.

The emerging landscape of exosomal CircRNAs in solid cancers and hematological malignancies.

Circular RNAs (circRNAs) are a type of recently discovered noncoding RNA. They exert their biological functions by competitively binding to microRNAs (miRNAs) as miRNA sponges, promoting gene transcription and participating in the regulation of selective splicing, interacting with proteins and being translated into proteins. Exosomes are derived from intracavitary vesicles (ILVs), which are formed by the inward budding of multivesicular bodies (MVBs), and exosome release plays a pivotal role in intercellular communication. Accumulating evidence indicates that circRNAs in exosomes are associated with solid tumor invasion and metastasis. Additionally, emerging studies in the last 1 ~ 2 years have revealed that exosomal circRNA also have effect on hematological malignancies. In this review, we outline the properties and biological functions of circRNAs and exosomes. In particular, we summarize in detail the mechanism and roles of exosomal circRNAs and highlight their application as novel biomarkers in malignant tumors.

Novel Insights Into MALAT1 Function as a MicroRNA Sponge in NSCLC.

The long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was initially found to be overexpressed in early non-small cell lung cancer (NSCLC). Accumulating studies have shown that MALAT1 is overexpressed in the tissue or serum of NSCLC and plays a key role in its occurrence and development. In addition, the expression level of MALAT1 is significantly related to the tumor size, stage, metastasis, and distant invasion of NSCLC. Therefore, MALAT1 could be used as a biomarker for the early diagnosis, severity assessment, or prognosis evaluation of NSCLC patients. This review describes the basic properties and biological functions of MALAT1, focuses on the specific molecular mechanism of MALAT1 as a microRNA sponge in the occurrence and development of NSCLC in recent years, and emphasizes the application and potential prospect of MALAT1 in molecular biological markers and targeted therapy of NSCLC.

Prenatal and postnatal traffic pollution exposure, DNA methylation in Shank3 and MeCP2 promoter regions, H3K4me3 and H3K27me3 and sociability in rats' offspring.

BACKGROUND: Road traffic air pollution is linked with an increased risk of autistic spectrum disorder (ASD). The aim of this study is to assess the effect of exposure to prenatal or postnatal traffic-related air pollution combining concomitant noise pollution on ASD-related epigenetic and behavioral alternations on offspring. METHODS: A 2 × 2 factorial analysis experiment was designed. Wistar rats were exposed at different sites (L group: green space; H group: crossroads) and timings (E group: full gestation; P group: 21 days after birth) at the same time, and air pollutants of nitrogen dioxide (NO2) and fine particles (PM2.5) were meanwhile sampled. On postnatal day 25, brains from offspring of each group were extracted to determine the levels of DNA methylation in Shank3 (three parts: Shank3_01, Shank3_02, Shank3_03) and MeCP2 (two parts: MeCP2_01, MeCP2_02) promoter regions, H3K4me3 and H3K27me3 after three-chamber social test. Meanwhile, the Shank3 and MeCP2 levels were quantified. RESULTS: The concentrations of PM2.5 (L: 58.33 µg/m3; H: 88.33 µg/m3, P < 0.05) and NO2 (L: 52.76 µg/m3; H: 146.03 µg/m3, P < 0.01) as well as the intensity of noise pollution (L: 44.4 dB (A); H: 70.1 dB (A), P < 0.001) differed significantly from 18:00 to 19:00 between experimental sites. Traffic pollution exposure (P = 0.006) and neonatal exposure (P = 0.001) led to lower weight of male pups on PND25. Male rats under early-life exposure had increased levels of Shank3 (Shank3_02: timing P < 0.001; site P < 0.05, Shank3_03: timing P < 0.001) and MeCP2 (MeCP2_01: timing P < 0.001, MeCP2_02: timing P < 0.001) methylation and H3K4me3 (EL: 11.94 µg/mg; EH: 11.98; PL: 17.14; PH: 14.78, timing P < 0.05), and reduced levels of H3K27me3 (EL: 71.07 µg/mg; EH: 44.76; PL: 29.15; PH: 28.67, timing P < 0.001; site P < 0.05) in brain compared to those under prenatal exposure. There was, for female pups, a same pattern of Shank3 (Shank3_02: timing P < 0.001; site P < 0.05, Shank3_03: timing P < 0.001) and MeCP2 (MeCP2_01: timing P < 0.05, MeCP2_02: timing P < 0.001) methylation and H3K4me3 (EL: 11.27 µg/mg; EH: 11.55; PL: 16.11; PH: 15.44, timing P < 0.001), but the levels of H3K27me3 exhibited an inverse trend concerning exposure timing. Hypermethylation at the MeCP2 and Shank3 promoter was correlated with the less content of MeCP2 (female: EL: 32.23 ng/mg; EH: 29.58; PL: 25.01; PH: 23.03, timing P < 0.001; site P < 0.05; male: EL: 31.05 ng/mg; EH: 32.75; PL: 23.40; PH: 25.91, timing P < 0.001) and Shank3 (female: EL: 5.10 ng/mg; EH: 5.31; PL: 4.63; PH: 4.82, timing P < 0.001; male: EL: 5.40 ng/mg; EH: 5.48; PL: 4.82; PH: 4.87, timing P < 0.001). Rats with traffic pollution exposure showed aberrant sociability preference and social novelty, while those without it behaved normally. CONCLUSIONS: Our findings suggest early life under environmental risks is a crucial window for epigenetic perturbations and then abnormalities in protein expression, and traffic pollution impairs behaviors either during pregnancy or after birth.

Preventing alloimmune rejection using circular RNA FSCN1-silenced dendritic cells in heart transplantation.

BACKGROUND: While heart transplantation is used as a standard treatment for heart failure, transplant rejection continues to pose a challenge. Recent evidence has shown that circular RNA (circRNA) is a new type of gene regulator in cell development. Our aim was to demonstrate that treatment with tolerogenic dendritic cells (Tol-DCs) generated by circular RNA FSCN1 (circFSCN1) silencing could prevent alloimmune rejection and prolong heart graft survival in heart transplantation. METHODS: Bone marrow-derived DCs were transfected with circFSCN1 siRNA in vitro. The circFSCN1 level was measured by qRT-PCR. DC maturation was determined by flow cytometry. Mixed lymphocyte reactions (MLRs) were conducted to assess the function of DCs to activate T cells and to generate regulatory T cells (Tregs). In situ RNA hybridization and fluorescent microscopy were performed to detect the distribution of circFSCN1 in DCs. A heterotopic allogeneic murine heart transplantation was conducted where recipients were pre-treated with donor derived circFSCN1-silenced Tol-DCs. Heartbeat was monitored to assess immune rejection. RESULTS: Exonic circFSCN1 was highly expressed in the cytoplasm of mature DCs. Knockdown of circFSCN1 using siRNA arrested DCs at an immature state, impaired DC's ability to activate T cells and enhanced Treg generation. Treatment with circFSCN1-silenced Tol-DCs prevented alloimmune rejection, prolonged allograft survival, reduced fibrosis, and induced Tregs in vivo. CONCLUSIONS: Knockdown of circFSCN1 induces Tol-DCs and treatment with these Tol-DCs prevents alloimmune rejection and prolongs allograft survival. This is a promising therapeutic target to combat transplant rejection in heart transplantation and increases our understanding of circRNA in the immune system.

Hair levels of heavy metals and essential elements in Chinese children with autism spectrum disorder.

BACKGROUND: Disproportional heavy metals and essential elements were reported in children with autism spectrum disorder (ASD) that is obscure in etiology. Inevitably, the association is biased by diet and environmental factors. METHODS: Fifty pairs, one with ASD and the other living together from the same special school with cerebral palsy (CP), were recruited in Hangzhou (China), aged from 2 to 11 years old (74.0 % male). All samples were divided into two subgroups: preschool-aged (2-5 years old) and school-aged (6-10 years old). Heavy metals (As, Hg, Pb) and essential elements (Al, Ca, Cu, Mg, Mn, Zn) in hair were quantified by inductively coupled plasma mass spectrometry analysis and flame atomic absorption spectroscopy. RESULTS: The children with ASD generally had lower hair levels of Mn (ASD 0.124 µg/g, CP 0.332 µg/g, P = 0.001) compared to the children with CP. After stratification for age, there were no significant differences detected in preschool-aged group. In school-aged group, the results exhibited the children with ASD had higher hair Pb (1.485 µg/g, 0.690 µg/g, P = 0.007) and Cu/Zn ratio (0.092, 0.060, P = 0.003), while hair Hg (0.254 µg/g, 0.353 µg/g, P = 0.016)、Mn (0.089 µg/g, 0.385 µg/g, P = 0.002)、Mg (17.81 µg/g, 24.53 µg/g, P = 0.014) and Zn (100.15 µg/g, 135.83 µg/g, P = 0.007) showed an opposite pattern. CONCLUSIONS: These results suggest an imbalance of Mn in Chinese children with ASD.

Circular RNA in colorectal cancer.

Circular RNA (circRNA) is a highly abundant type of single-stranded non-coding RNA. Novel research has discovered many roles of circRNA in colorectal cancer (CRC) including proliferation, metastasis and apoptosis. Furthermore, circRNAs also play a role in the development of drug resistance and have unique associations with tumour size, staging and overall survival in CRC that lend circRNAs the potential to serve as diagnostic and prognostic biomarkers. Among cancers worldwide, CRC ranks second in mortality and third in incidence. In order to have a better understanding of the influence of circRNA on CRC development and progression, this review summarizes the role of specific circRNAs in CRC and evaluates their potential value as therapeutic targets and biomarkers for CRC. We aim to provide insight in the development of therapy and clinical decision-making.

The role of miR-711 in cardiac cells in response to oxidative stress and its biogenesis: a study on H9C2 cells.

BACKGROUND: Oxidative stress results in cell apoptosis/death and plays a detrimental role in disease development and progression. Stressors alter the miRNA expression profile and miRNAs play a role in the cell response to stress. We previously showed that miR-711 is significantly over-expressed in extended cold ischemia reperfusion injured hearts in heart transplant. In this study, we aimed to investigate the role of miR-711 in cardiac cell damage in response to oxidative stress and how miR-711 is regulated. METHODS: Rat cardiac cell line H9c2 cells were cultured and exposed to oxidative conditions (Antimycin A (AA), H2O2, CoCl2, or cold hypoxia/reoxygenation (H/R)) in vitro. H9c2 cells were transfected with miR-711 mimics, miR-711 inhibitors, or small interference RNA, using transfection reagents. The expression of miR-711 was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell apoptosis/death was detected by flow cytometry and an IncuCyte system. Mitochondrial damage was detected by measuring the mitochondria membrane potential by flow cytometry. Gene expression was detected by qRT-PCR at the mRNA level and Western blotting and immunocytochemistry staining at the protein level. RESULTS: We found that miR-711 was significantly up-regulated in cells treated with H2O2, AA, CoCl2, and cold H/R. Over-expression of miR-711 increased cell apoptosis/death induced by AA and H/R whereas cell death was reduced by miR-711 inhibitors. MiR-711 induced cell death through negative regulation of angiopoietin 1 (Ang-1), fibroblast growth factor 14 (FGF14) and calcium voltage-gated channel subunit alpha1C (Cacna1c) genes. Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. CONCLUSION: Oxidative stress increases the expression of miR-711. Over-expression of miR-711 induces cell apoptosis/death. HIF-1α and NFКB regulate miR-711 in H9c2 cells during oxidative stress. miR-711 is a new target for preventing oxidative stress.

Plk2 Regulated by miR-128 Induces Ischemia-Reperfusion Injury in Cardiac Cells.

Ischemia-reperfusion (I/R) injury occurs during cardiac surgery and is the major factor leading to heart dysfunction and heart failure. Our previous study showed that gene and microRNA expression profiles are altered in heart grafts with extended I/R injury. In this study, we, for the first time, demonstrated that I/R injury upregulates the expression of Polo-like kinase 2 (Plk2) but decreases miR-128 expression in heart cells both in vitro and in vivo. Silencing Plk2 using small interfering RNA (siRNA) protects cells from Antimycin A-induced cell apoptosis/death. Silencing Plk2 also decreases phosphorylated p65 expression but increases Angiopoietin 1 expression. In addition, Plk2 is negatively regulated by miR-128. miR-128 exerts a protective effect on cell apoptosis similar to Plk2 siRNA in response to I/R stress. Methylation inhibitor 5-azacytidine (5-AZ) increases the expression of miR-128 and subsequently reduces Plk2 expression and cell apoptosis. In conclusion, this study demonstrated that Plk2 regulated by miR-128 induces cell apoptosis/death in response to I/R stress through activation of the nuclear factor κB (NF-κB) signal pathway. miR-128 and Plk2 are new targets for preventing cardiac I/R injury or oxidative stress-mediated injury.

LncRNA FOXD2-AS1 Regulates miR-25-3p/Sema4c Axis To Promote The Invasion And Migration Of Colorectal Cancer Cells.

PURPOSE: Although the roles of lncRNA FOXD2-AS1 have been investigated in many types of cancers including colorectal cancer (CRC), its functionality remains to be further investigated. Analysis of the TCGA data set revealed that FOXD2-AS1 was up-regulated in CRC tissues. This study aimed to analyze the function of FOXD2-AS1 in CRC. METHODS: FOXD2-AS1 expression was detected by qPCR. A 5-year follow-up study was performed to analyze the prognostic value of FOXD2-AS1 for CRC. Overexpression experiments were performed to analyze the interactions among FOXD2-AS1, miR-25-3p and Sema4C. Transwell assays were performed to analyze cell invasion and migration. RESULTS: In this study, we further confirmed the up-regulation of FOXD2-AS1 in CRC patients and showed that high FOXD2-AS1 level predicted poor survival. Bioinformatics analysis showed that miR-25-3p may bind FOXD2-AS1, while over-expression experiments showed no effects on each other's expression. Instead, FOXD2-AS1 over-expression led to the up-regulate Sema4C, which is a target of miR-25-3p. Transwell assay showed that FOXD2-AS1 and Sema4C over-expression led to the increased invasion and migration rates of CRC cells. MiR-25-3p plays the opposite role and attenuated the effects of FOXD2-AS1 and Sema4C over-expression. CONCLUSION: FOXD2-AS1 may regulate the miR-25-3p/Sema4C axis to promote the invasion and migration of CRC cells.

LncRNA MALAT1 negatively regulates MDSCs in patients with lung cancer.

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive functions and contribute to the formation of the tumor microenvironment. Long non-coding (Lnc) RNAs are highly important factors associated with tumors and may be used as markers for tumor diagnosis, which is valuable for targeted therapy. LncRNA MALAT1 is expressed in various tissues and plays a critical role in cell proliferation, including tumorigenesis and metastasis. However, the role of MALAT1 in MDSCs is unclear. In this study, we observed an increased proportion of MDSCs and elevated levels of the related molecule arginase-1 (ARG-1) in peripheral blood mononuclear cells (PBMCs) obtained from lung cancer patients. The proportion of CD8+ cytotoxic T lymphocyte (CTL) was significantly decreased in PBMCs from lung cancer patients. Moreover, the proportion of CTL cells was negatively correlated with the proportion of MDSCs. Furthermore, MALAT1 levels were decreased in PBMCs from lung cancer patients. The relative expression of MALAT1 was moderate negatively correlated with the proportion of MDSCs. In vitro results indicate that the knockdown of MALAT1 significantly increased the proportion of MDSCs. Our data provide the first evidence that lncRNA MALAT1 negatively regulates MDSCs and is decreased in PBMCs from lung cancer patients.