Role In Many Pathophysiological Processes Research Articles

ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells

Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored.Firstly, we assessed cell viability, proliferation, invasion, and migration using three cell lines (HuCCT-1, QBC399, and RBE) to explore the biological characteristics of ROR1-AS1 in CCA. Secondly, to determine the in vivo effect of ROR1-AS1 on tumor growth, ROR1-AS1 knockdown (KD) HuCCT-1 cells were subcutaneously injected into nude mice to evaluate tumor growth. Finally, we conducted a bioinformatic analysis to confirm the role of ROR1-AS1 in the prognosis and immunity of CCA.In this study, we found that lncRNA ROR1-AS1 was increased in CCA samples and patients with higher ROR1-AS1 expression had a shorter overall survival period. siRNA-mediated KD of ROR1-AS1 significantly reduced cell proliferation and inhibited the migration of CCA cells. In addition, ROR1-AS1 KD HuCCT-1 cells injected into nude mice grew slower than normal CCA cells.In summary, our results show that ROR1-AS1 can promote CCA progression and might serve as a new target for diagnosis and treatment of CCA.

Methylthio‐substituted coumarin‐based fluorescent probe for highly specific and fast detection of hypochlorite and bioimaging application

AbstractHypochlorite is a kind of endogenously produced reactive oxygen species (ROS) in the human immune system and plays a crucial role in many pathophysiological processes. In this work a novel fluorescent probe derived from 6‐methylthio coumarin was designed and synthesised for detection of hypochlorite in acetonitrile/phosphate‐buffered saline (MeCN/PBS) (1:1, v/v, pH 7.4) medium. The probe displayed high specificity toward hypochlorite over other ROS analytes, rapid response to hypochlorite within 30 s, and a broad applicable range of pH 3–8. The detection limit was calculated to be 1.48 μM. Application of this probe for in vitro Hecat cell imaging to detect hypochlorite ions was confirmed. A sensing mechanism based on thioether to sulfoxide oxidation by hypochlorite was proposed and demonstrated. The study presented an effective approach for construction of highly efficient hypochlorite chemosensors from hydrophilic methylthio‐substituted coumarins considering their facile access.

Cell Migration in Three Dimensions.

Cell migration plays an essential role in many pathophysiological processes, including embryonic development, wound healing, immunity, and cancer invasion, and is therefore a widely studied phenomenon in many different fields from basic cell biology to regenerative medicine. During the past decades, a multitude of increasingly complex methods have been developed to study cell migration. Here we compile a series of current state-of-the-art methods and protocols to investigate cell migration in a variety of model systems ranging from cells, organoids, tissue explants, and microfluidic systems to Drosophila, zebrafish, and mice. Together they cover processes as diverse as nuclear deformation, energy consumption, endocytic trafficking, and matrix degradation, as well as tumor vascularization and cancer cell invasion, sprouting angiogenesis, and leukocyte extravasation. Furthermore, methods to study developmental processes such as neural tube closure, germ layer specification, and branching morphogenesis are included, as well as scripts for the automated analysis of several aspects of cell migration. Together, this book constitutes a unique collection of methods of prime importance to those interested in the analysis of cell migration.

Characterization of the enzymatic properties of human RNPEPL1/aminopeptidase Z.

It is now evident that the M1 family of aminopeptidases play important roles in many pathophysiological processes. Among them, the enzymatic properties of arginyl aminopeptidase-like 1 (RNPEPL1) are characterized only by its truncated form. No peptide substrate has been identified. To characterize the enzymatic properties of RNPEPL1 in more detail, the full-length protein was expressed in Escherichia coli and purified to homogeneity. The full-length RNPEPL1 showed rather restricted substrate specificity and basic amino acid preference towards synthetic substrates, which was different from the previously reported specificity characterized by the truncated form. Searching for peptide substrates, we found that several peptides, such as Met-enkephalin and kallidin, were cleaved. RNPEPL1 cleaved bradykinin to de-[Arg]-bradykinin despite the presence of proline at the P2'-position. The enzyme cleaved Met-enkephalin but not dynorphin A1-17. Similar to aminopeptidase B, the full-length RNPEPL1 showed basic amino acid preference towards both synthetic and peptide substrates. In addition to the unusual cleavage of bradykinin, this enzyme shows chain length-dependent cleavage of peptide substrates sharing N-terminal amino acid sequence. This is the first study to report the enzymatic properties of the full-length human RNPEPL1 as an aminopeptidase enzyme.

Multiple circRNAs regulated by QKI5 conjointly spongemiR-214-3p to antagonize bisphenol A-inducedspermatocyte toxicity.

Although circular RNAs (circRNAs) are found to play important roles in many pathophysiological processes, the canonical theory that they act as microRNA sponges is now more and more challenged, given that most circRNAs only have few binding sites in a particular microRNA. Our previous study revealed that some up-regulated circRNAs play protective roles in bisphenol A (BPA)-induced toxicity in GC-2 germ cells. Here by CCK-8 assay, apoptosis assay, qRT-PCR and western blot analysis, we further discover that circRNAs (represented by circDcbld2, circMapk1 and circTbcld20) can cooperatively sponge miR-214-3p and then up-regulate AKT1 in ameliorating BPA-induced reproductive toxicity. They share binding sites with miR-214-3p and collectively reinforce the sponging effects. In addition, the upstream regulation mechanism, proven by bioinformatics analysis and in vitro gain- and loss-of-function study, shows that down-regulation of RNA binding protein QKI5 after BPA exposure can increase the expressions of these protective circRNAs, and thus activate the cell protective process. The QKI5-circDcbld2/circMapk1/circTblcd20-miR-214-3p-AKT1 axis ameliorates the toxic effect of BPA on GC-2 cells. Many other circRNAs up-regulated upon BPA treatment and QKI5 down-regulation also show binding sites with miR-214-3p. Thus the above axis may also be extrapolated to other circRNAs. Our results enrich the context of circRNA sponge mode and may provide new ideas in future multiple nucleic acid therapy.

The impact of BMI on the response to immunotherapy in lung cancer.

e21003 Background: Over the past few years immunotherapy was incorporated in the first line treatment for advanced lung cancer. Obesity leads to a state of low grade chronic inflammation and plays a role in many pathophysiological processes including tumorigenesis. Recently evidence indicates that obesity and related inflammatory state may also impact the efficacy of immunotherapy. Methods: We conducted a retrospective study to look at the impact of body mass index (BMI) on the outcomes in patients with advanced lung cancer treated with immune check point inhibitors (ICI). According to their baseline BMI, patients were grouped into obese (BMI ≥ 30, n = 54) and non-obese (BMI < 30, n = 158). In another comparison using 25 as BMI cut off, patients were grouped into higher BMI (BMI ≥ 25, n = 105) and lower BMI (BMI < 25, n = 107). Results: From June 2012 to December 2020, 212 patients from our institute were included in this study. The median age was 64.5, average BMI was 26.4 kg/m2, and 52% male sex. Median follow-up time in this study was 21.7 months. Patients with higher BMI using 25 as cut off had longer progression free survival (PFS) (8.1 months vs 5.3 months, p = 0.0034). Overall survival (OS) was better in higher BMI group than lower BMI group (10.8 months vs 5.9 months, p = 0.0008). The differences of PFS and OS for obese and non-obese groups were not statistically different (11.1 months vs 5.9 months, p = 0.157 for PFS; 12.0 months vs 6.9 months, p = 0.1512 for OS.). Conclusions: Our results suggest that excess weight may be associated with favorable PFS and OS in advanced lung cancer patients treated with ICI. Future studies are needed to investigate the underlying mechanism of this association.

Hydrogen Sulfide Biology and Its Role in Cancer.

Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.

NCLX expression regulation by mild stress conditions

Mitochondrial matrix Ca2+ efflux is largely mediated by the mitochondrial Na+/Ca2+ exchanger (NCLX), directly coupling mitochondrial Ca2+ and Na+ handling. NCLX has been shown to play a central role in many pathophysiological processes, including colorectal tumor metastasis, and Parkinson’s and Alzheimer diseases. Indeed, sporadic Alzheimer´s disease patients had decreased frontal cortex NCLX levels, an effect recapitulated in mouse models. However, transcriptional mechanisms specifying its functional states has not been clearly defined. Here, we aimed to investigate how NCLX expression is regulated. NCLX mRNA was consistently found to be increased after mild stressful events, including scrambled siRNA transfection and control adenoviral vector transduction. We then hypothesized that NCLX gene expression was controlled by a stress‐sensitive pathway. Indeed, serum‐deprived astrocytes and mouse embryonic fibroblasts (MEFs) showed an increase in NCLX mRNA levels, an effect that was even further modulated by incubation with thapsigargin or H2O2, indicating expression sensitivity to a wide variety of stress signals. Here, we took advantage of a genome‐wide approach using available epigenomics datasets, and transcriptomic data to pinpoint transcriptional factors that orchestrate NCLX gene expression upon homeostatic conditions in astrocytes. We identified promoter‐distal enhancer‐like elements in forebrain mouse and primary astrocytes using chromatin immunoprecipitation high‐throughput sequencing (ChIP‐seq) data marked by histone acetylation of lysine 27 (H3K27ac). We also used a public ATAC‐seq to define a coincident region with accessible chromatin. Still, transcription factor binding sites uncovered through sequence‐based single site analysis of the NCLX gene indicated several putative transcription factors, including many components of the NF‐κB family. In parallel, public RNA‐seq databases were mined for patterns that were correlated with transcription factor known effects, before proceeding with binding confirmation through ChIP‐PCR. In summary, we were able to build a foundation to test the modulation of NCLX expression. This proof‐of‐concept of NCLX stress‐induced mechanism may be further explored as a tool for targeting cellular Na+/Ca2+signaling, mitochondrial function, and metabolism.

Tanreqing Injection Attenuates Macrophage Activation and the Inflammatory Response via the lncRNA-SNHG1/HMGB1 Axis in Lipopolysaccharide-Induced Acute Lung Injury.

The etiology of acute lung injury (ALI) is not clear, and the treatment of ALI presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of ALI and to define the target gene of Tanreqing (TRQ), which is a traditional Chinese medicine formula composed of five medicines, scutellaria baicalensis, bear bile powder, goat horn powder, honeysuckle and forsythia. Macrophage activation plays a critical role in many pathophysiological processes, such as inflammation. Although the regulation of macrophage activation has been extensively investigated, there is little knowledge of the role of long noncoding RNAs (lncRNAs) in this process. In this study, we found that lncRNA-SNHG1 expression is distinctly regulated in differently activated macrophages in that it is upregulated in LPS. LncRNA-SNHG1 knockdown attenuates LPS-induced M1 macrophage activation. The SNHG1 promoter was bound by NF-κB subunit p65, indicative of SNHG1 being a direct transcriptional target of LPS-induced NF-κB activation. SNHG1 acts as a proinflammatory driver that leads to the production of inflammatory cytokines and the activation of macrophages and cytokine storms by physically interacting with high-mobility group box 1 (HMGB1) in ALI. TRQ inhibited NF-κB signaling activation and binding of NF-κB to the SNHG1 promoter. In conclusion, this study defined TRQ target genes, which can be further elucidated as mechanism(s) of TRQ action, and provides insight into the molecular pathogenesis of ALI. The lncRNA-SNHG1/HMGB1 axis is an ideal therapeutic for ALI treatment.

A benzocoumarin-based fluorescent probe for highly specific ultra-sensitive fast detecting endogenous/exogenous hypochlorous acid and its applications

Hypochlorous acid (HOCl) is widely used in daily production and life. It is also a kind of endogenously produced reactive oxygen species (ROS) in the human immune system, plays a crucial role in many pathophysiological processes. This work designed and synthesized a novel based on benzocoumarin fluorescent probe BL for specific detection HOCl. BL has brilliant selectivity, high sensitivity (5.64 nM), fast response (60 s), moderate water-solubility. The intramolecular charge transfer (ICT) sensing mechanism of BL has been verified by fluorescence, UV, MS, and density functional theory (DFT) calculations. BL can make into a solid-state visual sensor to detect HOCl conveniently. BL was also applied to detect HClO spiked in tap water, 84 disinfectants, lake water, and satisfying recovery rates. Finally, BL was low toxic and used to track the variations of endogenous/exogenous HClO in living cells successfully. Totally, BL provides a powerful and reliable monitoring tool to reveal the biological functions of HOCl and ensure safe use.

Recent Progress of Ferroptosis in Lung Diseases.

Ferroptosis is a new form of programmed cell death due to iron-dependent excess accumulation of lipid peroxides and differs from other programmed cell deaths in morphological and biochemical characteristics. The process of ferroptosis is precisely regulated by iron metabolism, lipid metabolism, amino acid metabolism, and numerous signaling pathways, and plays a complex role in many pathophysiological processes. Recent studies have found that ferroptosis is closely associated with the development and progression of many lung diseases, including acute lung injury, pulmonary ischemia-reperfusion injury, lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Here, we present a review of the main regulatory mechanisms of ferroptosis and its research progress in the pathogenesis and treatment of lung diseases, with the aim of providing new ideas for basic and clinical research of lung-related diseases.

A morpholino hydrazone-based lysosome-targeting fluorescent probe with fast response and high sensitivity for imaging peroxynitrite in living cells

Peroxynitrite (ONOO−) plays important roles in many pathophysiological processes and its subcellular detection draws increasing attention. In this study, we designed and prepared a novel lysosome-targetable fluorescent probe (E)-2-(benzo[d]thiazol-2- yl)-4-methyl-6-((morpholinoimino)methyl)phenol (BMP) for selective detection of ONOO− in living systems by incorporating a reactive morpholino hydrazone as new ONOO− response site into a benzothiazole derivative as fluorophore. After reaction with ONOO−, an obvious fluorescence increase (83-fold) was observed accompanied with distinct dual colorimetric and fluorescence changes. Probe BMP displayed the merits of fast response (<3 s), ultrasensitivity (LOD = 6 nM) and high selectivity towards ONOO− over other physiological species including ROS/RNS. Most importantly, the probe was capable of imaging ONOO− in lysosomes of living cells with good cell permeation and negligible cytotoxicity. Therefore, this research provides an effective tool to study the functions of ONOO− in lysosomes.

The Hippo pathway: a renewed insight in the craniofacial diseases and hard tissue remodeling.

The Hippo pathway plays an important role in many pathophysiological processes, including cell proliferation and differentiation, cell death, cell migration and invasion. Because of its extensive functions, Hippo pathway is closely related to not only growth and development, but also many diseases, including inflammation and cancer. In this study, the role of Hippo pathway in craniofacial diseases and hard tissue remodeling was reviewed, in attempting to find new research directions.

MicroRNA-338 in MSCs-derived exosomes inhibits cardiomyocyte apoptosis in myocardial infarction.

Myocardial infarction (MI) is caused by myocardial ischemia and hypoxia, which causes irreversible damage to the myocardium and seriously endangers human health. Exosomes are small, monolayer-structured extracellular vesicles that transport proteins, lipids, mRNAs, and miRNAs between cells. Mesenchymal stem cells (MSCs) can secrete a large number of exosomes and play a role in many pathophysiological processes. The purpose of this paper was to investigate the role of exosomal microRNA-338 (miR-338) in MI and its underlying mechanism of action. We transfected rat bone marrow-derived MSCs with miR-338 mimic or negative control and extracted exosomes secreted by MSCs. Expression of miR-338 in MSCs, exosomes, and H9c2 cells co-cultured with exosomes was detected by PCR. Then, we treated H9c2 cells with H2O2. We transfected miR-338 inhibitor into H9c2 cells co-cultured with exosomes to further study the function of miR-338. Apoptosis of H9c2 cells were observed by Western blot, flow cytometry, and cell staining. We also established a MI rat model to study the function in vivo and injected exosomes in the myocardium. Seven days later, we used echocardiography to detect the heart function of rats. MiR-338 was upregulated in MSCs transfected with miR-338 mimic, exosomes, and H9c2 cells co-cultured with exosomes. When H9c2 cells were co-cultured with exosomes overexpressing miR-338, the expression of Bax was decreased while the expression of Bcl-2 was increased, and the apoptosis rate was also decreased as shown in flow cytometry, and the amount of caspase3 fluorescence was also decreased. Cardiac function was markedly improved after intramyocardial injection of exosomes overexpressing miR-338 in rats. It was demonstrated using computational tools, Western blot, and Luciferase reporter gene experiments that miR-338 could regulate JNK pathway via targeting MAP3K2. Exosomal miR-338 can inhibit cardiomyocyte apoptosis and improve cardiac function in rats with myocardial infarction by regulating MAP3K2/JNK signaling pathway.

Molecular Mechanisms of Ferroptosis and Its Role in Pulmonary Disease.

Ferroptosis is a new mode of cell death that is characterized by the excessive accumulation of iron and lipid peroxides. It has unique morphological changes and disparate biochemical features and plays an intricate role in many pathophysiological processes. A great deal of researches confirms that ferroptosis can be regulated by numerous molecules through different mechanisms, supporting great potentials for novel pharmacological therapeutics. Recently, several studies reveal that ferroptosis is also closely associated with the initiation and development of respiratory disease. Understanding the specific mechanism, the molecular trait of ferroptosis and their relationship with pulmonary disease could provide significant references regarding effective treatment of these obstinate disease.

S1P/S1P Receptor Signaling in Neuromuscolar Disorders.

The bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P), and the signaling pathways triggered by its binding to specific G protein-coupled receptors play a critical regulatory role in many pathophysiological processes, including skeletal muscle and nervous system degeneration. The signaling transduced by S1P binding appears to be much more complex than previously thought, with important implications for clinical applications and for personalized medicine. In particular, the understanding of S1P/S1P receptor signaling functions in specific compartmentalized locations of the cell is worthy of being better investigated, because in various circumstances it might be crucial for the development or/and the progression of neuromuscular diseases, such as Charcot–Marie–Tooth disease, myasthenia gravis, and Duchenne muscular dystrophy.

Stanniocalcin-1 mediates negative regulatory action of epidermal layer on expression of matrix-related genes in dermal fibroblasts.

Dermal–epidermal interaction plays a role in many pathophysiological processes, such as tumor invasion and psoriasis, as well as wound healing, and is mediated at least in part by secretory factors. In this study, we investigated the factor(s) involved. We found that stanniocalcin‐1 (STC1), a cytokine, is expressed at the basal layer of epidermis. Knockdown of STC1 with siRNA in HaCaT cells decreased matrix metalloproteinase 1 (MMP1) expression, suggesting that STC1 serves as an autocrine factor, maintaining MMP1 mRNA expression in the epidermal layer. In dermal fibroblasts, STC1 increased MMP1 mRNA expression and decreased collagen1A1 and elastin mRNA expression. These actions were inhibited by SP600125, a jun kinase (JNK) inhibitor. Nuclear translocation of AP‐1, a downstream signal of JNK, was implicated in the actions of STC1. In a coculture system of HaCaT cells and fibroblasts, used as a model of dermal–epidermal interaction, knockdown of STC1 in HaCaT cells with siRNA reduced the negative effects (i.e., induction of MMP1 and decrease of collagen1A1 and elastin) of STC1 on fibroblasts. These results suggest that STC1 secreted from the epidermal layer is a mediator of dermal–epidermal interaction.

Tubulin in Platelets: When the Shape Matters.

Platelets are anuclear cells with a short lifespan that play an essential role in many pathophysiological processes, including haemostasis, inflammation, infection, vascular integrity, and metastasis. Billions of platelets are produced daily from megakaryocytes (platelet precursors). Despite this high production, the number of circulating platelets is stable and, under resting conditions, they maintain their typical discoid shape thanks to cytoskeleton proteins. The activation of platelets is associated with dynamic and rapid changes in the cytoskeleton. Two cytoskeletal polymer systems exist in megakaryocytes and platelets: actin filaments and microtubules, based on actin, and α- and β-tubulin heterodimers, respectively. Herein, we will focus on platelet-specific tubulins and their alterations and role of the microtubules skeleton in platelet formation (thrombopoiesis). During this process, microtubules mediate elongation of the megakaryocyte extensions (proplatelet) and granule trafficking from megakaryocytes to nascent platelets. In platelets, microtubules form a subcortical ring, the so-called marginal band, which confers the typical platelet discoid shape and is also responsible for changes in platelet morphology upon activation. Molecular alterations in the gene encoding β1 tubulin and microtubules post-translational modifications may result in quantitative or qualitative changes in tubulin, leading to altered cytoskeleton reorganization that may induce changes in the platelet number (thrombocytopenia), morphology or function. Consequently, β1-tubulin modifications may participate in pathological and physiological processes, such as development.

Dialysate copeptin and peritoneal transport in incident peritoneal dialysis patients

PurposeSystemic and intraperitoneal inflammation are characteristic features of patients with end-stage renal disease undergoing chronic peritoneal dialysis (PD). Arginine vasopressin (AVP) and its surrogate marker copeptin play important roles in many pathophysiological processes in chronic kidney disease. The aim of this study was to assess if copeptin concentrations in plasma and dialysate were related to peritoneal transport parameters and residual renal function (RRF) in incident PD patients.MethodsIn 37 clinically stable incident PD patients (mean age 50 years, 68% women, 32% diabetes), a 4 h peritoneal equilibration test (PET) was performed 4–6 weeks after the onset of PD. Plasma (at 2 h of PET) and dialysate (at 4 h) concentrations of copeptin, high-sensitivity C-reactive protein and interleukin-6 (IL-6) were determined.ResultsPlasma (80.7 ± 37.3 pg/mL) and dialysate (33.2 ± 18.0 pg/mL) concentrations of copeptin were correlated (Rs = 0.52, p = 0.001). Plasma and dialysate copeptin concentrations were negatively correlated with renal function as assessed by renal Kt/V (Rs = − 0.38; p = 0.021 and Rs = − 0.33; p = 0.047, respectively). At PET, dialysate copeptin negatively correlated with D/P creatinine (Rs = − 0.35, p = 0.033), and positively with D/D0 glucose (Rs = 0.33, p = 0.045) and ultrafiltration (Rs = 0.37, p = 0.024). Multivariate analysis showed that low dialysate copeptin (β = –0.30, p = 0.049) and high dialysate IL-6 (β = + 0.40, p = 0.012) were independent determinants of higher D/P creatinine.ConclusionsDialysate copeptin was negatively associated with D/P creatinine in incident PD patients suggesting a potential influence of copeptin or AVP on peritoneal solute transport rate that might involve vasoactive mechanisms.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-\u03baB signaling

BackgroundXenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. However, the role of XPR1 in human cancers has not yet been characterized.MethodsReal-time PCR and western blotting assay were used to measure the expression of XPR1 in tongue squamous cell carcinoma (TSCC) tissues. Expression of XPR1 and p65 in clinical specimens was analyzed using immunohistochemical assay. The function of XPR1 on progression of TSCC was explored using in vitro and in vivo experiments. The molecular mechanism by which XPR1 helps to cancer progression was investigated by luciferase reporter activity, ELISA, PKA activity assay, immunofluorescence, western blotting and qPCR assay.ResultsHerein, we find that XPR1 is markedly upregulated in TSCC tissues compared to normal tongue tissues. High expression of XPR1 significantly correlates with the malignant features and poor patient survival in TSCC. Ectopic expression of XPR1 increases, while silencing of XPR1 reduces the proliferation, invasion and anti-apoptosis capacities of TSCC cells. Importantly, silencing of XPR1 effectively inhibits the tumorigenecity of TSCC cells. Moreover, we identified that XPR1 increased the concentration of intracellular cAMP and activated PKA. Thus, XPR1 promoted phosphorylation and activation of NF-κB signaling, which is required for XPR1-mediated oncogenic roles and significantly correlates with XPR1 expression in clinical specimens.ConclusionsThese findings uncover a critical role of XPR1 in TSCC progression via activation of NF-κB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target.