Mediator Of Migration Research Articles

Precursor Film Mediated Spontaneous Migration of Condensed Microdroplets

Precursor Film Mediated Spontaneous Migration of Condensed Microdroplets

PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity

While the function of extracellular region of programmed death ligand 1 (PD-L1) through its interactions with PD-1 on T cells is well studied, little is understood regarding the small intracellular domain of PD-L1. Here, we outline a major role for PD-L1 intracellular signaling in the control of DC migration from the skin to the draining lymph node (dLN). Using a mutant mouse model we identified a TSS signaling motif within the intracellular domain of PD-L1. While loss of the TSS motif had no impact on PD-L1 expression, this motif proved critical for chemokine mediated DC migration to the dLN during inflammation. The loss of DC chemokine mediated migration, in the PD-L1 TSS mutant, led to a significant decline in T cell priming when DC trafficking was required for antigen delivery to the dLN. Finally, the TSS motif was required for ERK phosphorylation and actin polymerization in DCs treated with chemokine.

NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin.

Angiogenesis relies on the ability of endothelial cells (ECs) to migrate over the extracellular matrix via integrin receptors to respond to an angiogenic stimulus. Of the two neuropilin (NRP) orthologs to be identified, both have been reported to be expressed on normal blood and lymphatic ECs, and to play roles in the formation of blood and lymphatic vascular networks during angiogenesis. Whilst the role of NRP1 and its interactions with integrins during angiogenesis has been widely studied, the role of NRP2 in ECs is poorly understood. Here we demonstrate that NRP2 promotes Rac-1 mediated EC adhesion and migration over fibronectin (FN) matrices in a mechanistically distinct fashion to NRP1, showing no dependence on β3 integrin (ITGB3) expression, or VEGF stimulation. Furthermore, we highlight evidence of a regulatory crosstalk between NRP2 and α5 integrin (ITGA5) in ECs, with NRP2 depletion eliciting an upregulation of ITGA5 expression and disruptions in ITGA5 cellular organization. Finally, we propose a mechanism whereby NRP2 promotes ITGA5 recycling in ECs; NRP2 depleted ECs were found to exhibit reduced levels of total ITGA5 subunit recycling compared to wild-type (WT) ECs. Our findings expose NRP2 as a novel angiogenic player by promoting ITGA5-mediated EC adhesion and migration on FN.

Paeoniflorin-6′-O-benzene sulfonate down-regulates CXCR4-Gβγ-PI3K/AKT mediated migration in fibroblast-like synoviocytes of rheumatoid arthritis by inhibiting GRK2 translocation

ObjectiveThis study aims to explore the effect of paeoniflorin-6′-O-benzene sulfonate (CP-25) on the migration of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) and the mechanism focused on CXCR4-Gβγ-PI3K/AKT signaling. MethodsHuman synovial tissues were collected from RA and osteoarthritis (OA) patients. Immunohistochemistry (IHC) and Western blot were used to detect the protein expression of CXCR4, GRK2, Gβγ, PI3K, p-PI3K, AKT and p-AKT. Transwell was adopted to analyse the migration of fibroblast-like synoviocytes (FLS). Co-immunoprecipitation (Co-IP) and laser scanning confocal microscopy (LSCM) were used to detect the combination of GRK2 and Gβγ, the combination of PI3K and Gβγ. ResultsThe expression level of CXCR4, GRK2, Gβγ, p-p85 and p-AKT were increased in RA synovial tissue according to the results of IHC and Western blot. In vitro, the migration of FLS was increased after stimulation of CXCL12, inhibition of Gβγ suppressed the migration and phosphorylation of p85 and AKT induced by CXCL12 in FLS, and CP-25 had the same effect as inhibition of Gβγ. The membrane expression of GRK2, Gβγ, PI3K and the combination of GRK2 and Gβγ, the combination of PI3K and Gβγ in FLS were increased after the stimulation of CXCL12, and CP-25 had an ability in reducing the membrane expression and the combination of these proteins. ConclusionExcessive migration of FLS in RA was associated with over-activation of PI3K/AKT signaling, and the activity of Gβγ was involved in the over-activation of PI3K/AKT. CP-25 down-regulated CXCR4-Gβγ-PI3K/AKT signals by inhibiting GRK2-Gβγ complex membrane translocation.

MiRNA-26a blocks interleukin-2-mediated migration and proliferation of non-small cell lung cancer cells via vascular cell adhesion molecule-1.

BackgroundLiteratures have confirmed role of inflammatory mediators like interleukin-2 (IL-2) in non-small cell lung cancer (NSCLC). microRNA-26a (miR-26a) is involved in variety of signaling pathways and functions as tumor suppressor and regulating the responsible genes at posttranscriptional level. The aim of study was to study the correlation of IL-2 and miR-26a in lung cancer (LC) cells.MethodsFor the study we selected 32 subjects reported for NSCLC and 20 with chronic obstructive pulmonary disease (COPD) as control in the present study. For in vitro analysis, H-460 and H-226 cell lines were selected and received treatment of varying dose of IL-2 to study the effect of IL-2 on expression of miR-26a and vascular cell adhesion molecule-1 (VCAM-1). miR-26a mimic and miR-26a inhibitor were transfected to study the effect on progression and migration of tumor cell as well as on levels of VCAM-1.ResultsWe evidenced that, expression of miR-26a was suppressed, whereas levels of IL-2 and VCAM-1 were increased in NSCLC tissues. IL-2 down-regulated the levels of miR-26a but upregulated the levels of VCAM-1 in H-460 and H-226 cells. miR-26a modulated the expression level of VCAM-1 via binding the 3'-UTR region. We found that miR-26a attenuated the migration and proliferation of H-460 and H-226 cells. IL-2 modulated the levels of miR-26a via activating p65 but not STAT-3.ConclusionsAll together, the finding of our study show that miR-26a blocks IL-2 mediated proliferation and migration of NSCLC via targeting VCAM-1.

Compensatory growth offsets poor condition in native trout populations

Abstract Compensatory growth—when individuals in poor condition grow rapidly to catch up to conspecifics—may be a mechanism that allows individuals to tolerate stressful environmental conditions, both abiotic and biotic. This phenomenon has been documented fairly widely in laboratory and field experiments, but evidence for compensatory growth in the wild is scarce. Cutthroat trout (Oncorhynchus clarkii subsp.) are cold‐water specialists that inhabit montane streams in western North America where seasonal conditions can be harsh and growth rates vary greatly among seasons. Understanding if individuals compensate for periods of reduced growth and body condition will improve understanding of the requirements of fish throughout their life‐cycle and across freshwater habitats. We quantified compensatory growth of juvenile cutthroat trout using extensive mark–recapture data from 11 stream populations (1,125 individuals) and two subspecies inhabiting a wide range of ecological settings in the northern Rocky Mountains, U.S.A. Our objectives were to determine how growth was linked across seasons and whether individuals behaviourally compensated for depressed body condition via emigration. Fish in relatively poor condition consistently demonstrated compensatory growth in mass during subsequent seasons. In contrast, fish in relatively better condition responded with positive growth in length during the summer signalling these fish may be better suited to headwater environments; no compensatory growth in length was found during the winter. Furthermore, there was no evidence that individual condition mediated migration tendencies of fish to seek more favourable habitat. Across a wide range of environmental conditions, we found consistent empirical support for compensatory growth in mass in the wild. A critical next step is to quantify how changing abiotic and biotic conditions influence the ability of stream fishes to compensate for locally or seasonally challenging conditions, thereby affecting long‐term resiliency, viability, and adaptation in the face of changing environmental conditions.

Cross-cultural Mediation in ELF Migration Contexts: Pedagogical Implications on ELT Multilingual Settings

ELF cross-cultural interactions and mediation processes in specialized migration settings are often characterized by ‘gatekeeping’ asymmetries between the participants involved challenging a successful meaning negotiation (Guido, 2008). The exploration of migration encounters (Sperti, 2017) is particularly useful in the analysis of naturally occurring dialogues among ELF users, since it shows how ELF speakers, engaged in intercultural interactions, appropriate the English language according to their own native linguacultural and paralinguistic schemata, and to specific pragmalinguistic purposes and processes. The multimodal investigation of the occurring hybridization processes is focused on (i) ELF redefinition of existing native paralinguistic correlates in the pragmalinguistic use of an ELF variation; and (ii) resulting L1 transfers affecting the performing of speech acts and the conversational composition and progress. The analysis reveals (a) the mediation of meaning, experience and intentionality in terms of resulting lexical, syntactical, and register performance; and (b) the role played by prosody and paralanguage in the mutual acceptance of speakers’ intentions, attitudes, and cognitive schemata, in spoken specialized discourse related to medical and legal integration, mediated migration narratives, cross-cultural conceptual representations and reception of traumatic experience. The heuristic approach applied to the analysis of data derived from the exploration of real plurilingual cross-cultural exchanges is particularly useful in the promotion of the conscious use of cross-cutting strategies as powerful learning tools embedded in the language learning process, with the ultimate aim of (i) investigating the possible impact of migration on teacher education, (ii) defining an ELF-aware pedagogical framework in plurilingual educational settings, and (iii) enhancing the development of learners’ skills in intercultural communication.

Newcastle disease virus mediated apoptosis and migration inhibition of human oral cancer cells: A probable role of \u03b2-catenin and matrix metalloproteinase-7

Cancer cell metastasis and its dissemination are most enigmatic and challenging aspects in the development of its therapeutics. Newcastle disease virus (NDV) is a well-studied avian paramyxovirus frequently isolated from birds and rarely from mammals. Since the first report of its oncolytic property, many NDV strains were studied for its effect in various cancer cells. In the present study, NDV strain Bareilly was characterized for its apoptotic potential and migration inhibition in human oral cancer cells. The NDV mediated apoptosis was confirmed by flow cytometry, DNA laddering, and immunoblotting. Moreover, NDV decreased the mitochondrial membrane potential suggesting an intrinsic pathway of apoptosis in oral cancer cells. NDV infection in oral cancer cells results in migration inhibition by a reduction in levels of MMP-7. MMP-7 is one of the key target genes of β-catenin. While overexpression of MMP-7 reversed the inhibitory effect of NDV mediated migration suggested its possible involvement. Wnt/β-catenin is an essential pathway for cell growth, differentiation, and metastasis. The involvement of the Wnt/β-catenin pathway in NDV infection has never been reported. Our results showed that NDV dysregulates Wnt/β-catenin by down-regulation of p-Akt and p-GSK3β leading to degradation of β-catenin. Furthermore, NDV infection leads to a reduction in cytoplasmic and nuclear levels of β-catenin. The study will provide us with a better insight into the molecular mechanism of NDV mediated oncolysis and the key cellular partners involved in the process.

Influence of SHH/GLI1 axis on EMT mediated migration and invasion of breast cancer cells

Sonic Hedgehog signaling is critical for breast morphogenesis and cancer. The present study was conducted to explore the influence of SHH/GLI1 axis on epithelial mesenchymal transition and invasion in breast cancer cells. SHH/GLI1 positive samples demonstrated high expression of Snail and Vimentin with relatively low expression of E-cadherin. Overexpression of Vimentin and Snail in SHH/GLI1 positive patients was also associated with poor overall survival. Interestingly, GANT61 (GLI1 inhibitor) exposure significantly reduced cell viability and induced apoptosis at 10 µM. Suppression of Hedgehog pathway either by CRISPR mediated SHH knock out or GANT61 altered regulation of EMT markers in breast cancer cells. Moreover, in-activation of SHH/GLI1 axis also significantly restricted cell migration and invasiveness. These findings suggest that targeting SHH/GLI1 axis alters expression of EMT markers and abrogates neoplastic invasion in breast cancer cells.

Reversible Modification of Ferromagnetism through Electrically Controlled Morphology

AbstractConverse magnetoelectric coupling in artificial multiferroics is generally modeled through three possible mechanisms: charge transfer, strain mediated effects or ion migration. Here the role played by electrically controlled morphological modifications on the ferromagnetic response of a multiferroic heterostructure, specifically FexMn1−x ferromagnetic films on piezoferroelectric PMN‐PT [001] substrates, is discussed. The substrates present, in correspondence to electrical switching, fully reversible morphological changes at the surface, to which correspond reproducible modifications of the ferromagnetic response of the FexMn1−x films. Topographic analysis by atomic force microscopy shows the formation of surface cracks (up to 100 nm in height) upon application of a sufficiently high positive electric field (up to 6 kV cm−1). The cracks disappear after application of negative electric field of the same magnitude. Correspondingly, in operando X‐ray magnetic circular dichroic spectroscopy at Fe edge in FexMn1−x layers and micro‐MOKE measurements show local variations in the intensity of the dichroic signal and in the magnetic anisotropy as a function of the electrically driven morphological state. This morphologic parameter, rarely explored in literature, directly affects the ferromagnetic response of the system. Its proof of electrically reversible modification of the magnetic response adds a new possibility in the design of electrically controlled magnetic devices.

PDGF regulated migration of mesenchymal stem cells towards malignancy acts via the PI3K signaling pathway.

Mesenchymal stem cells (MSCs) have been described in breast cancer models to migrate towards carcinoma and integrate into tumor associated stroma supporting tumor growth, increasing their metastatic potency and contributing to tumor-angiogenesis. Platelet-derived growth factor (PDGF) isoforms (AA, BB, CC) stimulate growth, survival and motility of MSCs and certain other cell types. Noteworthy, breast carcinomas are known to express PDGF. We aim to further shed light on i) the relevance of the different PDGF isoforms on adipose tissue derived stem cells (ASCs) migration and ii) the underlying pathway dependent on PDGF stimulation. Breast cancer cell lines were purchased and ASC's were isolated from murine subcutaneous adipose tissue. The transmigration of ASC's towards the PDGF-isoforms was assessed by using recombinant human PDGF-AA, PDGF-BB and PDGF-CC in a trans-well culture dish system. Transmigrated ASC's were quantified in 5 randomly selected fields per condition using fluorescence microscopy after calcein-staining. PDGF-BB depended transmigration of ASC's was verified by downregulation and overexpression of PDGF-BB in breast cancer cell line using lentiviral vectors. In addition, a PI3-kinase inhibitor (LY294002) and a MAP-kinase inhibitor (PD98059) were used to identify the pathway involved in the PDGF-BB mediated migration of ASC's towards tumor. ASC's transmigration significantly increased towards PDGF AA at 50 ng and only showed further increase by 500 ng which was similar to cell behavior when exposed to PDGF CC. In comparison, PDGF-BB significantly increased ASC's transmigration already at a low level of 5 ng with further significant increase for 20 ng and 40 ng. Cell transmigration was blocked with PDGFR-α antibodies but only for PDGF-AA and PDGF-CC whereas PDGFR-β blockage showed a significant effect on transmigration for PDGF-BB and PDGF-CC but not for PDGF-AA. Neutralizing antibodies in combination with PDGF receptor blockage confirmed findings. In addition, only PI3-kinase inhibitor but not the MEK-1 selective inhibitor caused a significant decrease of transmigration for ASCs towards breast cancer cells. The transmigration of ASC's is most significantly enhanced by PDGF-BB via the PI3-kinase pathway. This data support that PI3-kinase is an important key player for MSC migration towards malignancy which need further research to prevent tumor progression in early disease stage.

Role of Leptin/Osteopontin Axis in the Function of Eosinophils in Allergic Rhinitis with Obesity.

Background Allergic rhinitis (AR) is characterized by tissue and blood eosinophilia. Previous studies showed enhanced eosinophilia in allergic rhinitis patients with obesity, suggesting an association between obesity and eosinophilia. However, the interaction and mechanism between obesity and eosinophilia is still unclear. Methods We recruited thirty AR children and 30 controls in this study. Expression of leptin and osteopontin (OPN) proteins in serum was detected, and correlation analysis with eosinophilia was performed. The effect of leptin or OPN on eosinophil apoptosis, adhesion, migration, and activation of eosinophil was examined. Ovalbumin-sensitized mice were established to prove the role of obesity on eosinophil regulation by leptin and OPN. Results We found that upregulated serum and nasal leptin and OPN expression in AR were positively correlated with eosinophilia and eosinophil cationic protein levels. Leptin or OPN inhibited eosinophil apoptosis, demonstrated as inhibited DNA fragmentation and phosphatidylserine (PS) redistribution (P < 0.05). Leptin and OPN promote expression of cluster of differentiation 18 (CD-18) and intercellular adhesion molecule 1 (ICAM-1) and inhibit expression of ICAM-1 and L-selectin by eosinophils, which contribute to the adhesion of eosinophils. Leptin and OPN mediated migration and activation of eosinophil through phosphatidylinositol-3-OH kinase (PI3K) pathway. Obese AR mice presented with more severe eosinophilia and symptoms compared with nonobese AR mice or control mice. Immunochemistry staining of leptin and OPN of nasal turbinate in obese AR mice was also stronger than those in nonobese AR mice or control mice. Anti-OPN, anti-leptin, and anti-α4 treatments reduce nasal eosinophilia inflammation and clinical symptoms in model mice. Conclusion Our results suggested that in an obese state, upregulation of leptin and OPN regulates apoptosis, adhesion, migration, and activation of eosinophils, and this process may be mediated by the PI3K and anti-α4 pathways.

Visible Light Mediated Aryl Migration by Homolytic C-N Cleavage of Aryl Amines.

The photocatalytic preparation of aminoalkylated heteroarenes from haloalkylamides via a 1,4-aryl migration from nitrogen to carbon, conceptually analogous to a radical Smiles rearrangement, is reported. This method enables the substitution of amino groups in heteroaromatic compounds with aminoalkyl motifs under mild, iridium(III)-mediated photoredox conditions. It provides rapid access to thienoazepinone, a pharmacophore present in multiple drug candidates for potential treatment of different conditions, including inflammation and psychotic disorders.

Amyloid Precursor Protein Underwent Proteolytic Cleavage by ADAM10 and Mediated Breast Cancer Growth and Migration

Background: Amyloid precursor protein (APP), best known for its association with Alzheimer disease, has recently suggested in breast cancer progression. However, the precise mechanism involved remains unclear. Here, we investigated the role of APP proteolytic cleavage in breast cancer functions. Methods: The presence of APP proteolytic cleavage products was examined in breast cancer cell lines. The functional roles of APP in breast cancer were studied in vitro and tumor xenograft model by siRNA interference. The effects of full length APP and the α-secretase cleaved ectodomain fragment, soluble APPα (sAPPα) were further investigated for their overexpression in breast cancers. The α-secretase involved was identified. The α-secretase expression together with APP was examined in clinical breast cancer. Results: We showed that APP underwent proteolytic cleavage in breast cancer cells to generate sAPPα. The sAPPα showed similar functional effects as the full length protein in breast cancer migration and proliferation. This proteolytic cleavage was mediated by ADAM10. Downregulation of APP and ADAM10 brought about similar functional effects. Overexpression of sAPPα could reverse the effects of ADAM10 downregulation. Interestingly, in patients with non-luminal breast cancer, APP and ADAM10 expression correlated with each other and their co-expression correlated with the worst outcome. Conclusions: These results indicated that the significance of APP cleavage on its oncogenic roles in breast cancer. ADAM10 demonstrated to be the key α-secretase. APP and ADAM10 co-expression associated with worse survival in non-luminal breast cancers. Targeting of APP or its processing by ADAM10 might be a promising treatment in these cancers. Funding: This study was supported by the Health and Medical Research Fund of Hong Kong (02130746). Declaration of Interests: All authors declare no conflict of interests. Ethics Approval Statement: The study was approved by Joint Chinese University of Hong Kong-New Territories East Cluster clinical research ethics committee.

Tu1762 - Inflammation-Activated Intestinal Muscularis Propria Muscle Cells Induce Integrin Mediated Mesenteric Adipocyte and Preadipocyte Migration—A Novel Mechanism for Creeping Fat Formation in Crohn's Disease

Tu1762 - Inflammation-Activated Intestinal Muscularis Propria Muscle Cells Induce Integrin Mediated Mesenteric Adipocyte and Preadipocyte Migration—A Novel Mechanism for Creeping Fat Formation in Crohn's Disease

Resveratrol and CXCR4 Mediated Migration of Brest Cancer Cell Lines

In the United States, breast cancer is one of the most common types of cancer among women, being the second cause of cancer‐related deaths. Despite early detection methods and available treatments, breast cancer incidence is increasing worldwide. Some malignant cells have the potential to migrate and invade, metastasizing to distant organs and tissues. Current treatments include surgery, chemotherapy, and radiotherapy. These treatments usually produce side effects that have a negative influence in the quality of life of the patients. Additional studies are necessary to identify candidate natural compounds targeting specific molecules and receptors expressed in breast cancer cells. For example, CXCR4 is a G protein‐coupled receptor known to be one of the major proteins involved in metastasis of breast cancer. It mediates migration towards tissues expressing its specific ligand CXCL12. Natural compounds such as resveratrol, a plant polyphenol commonly found in grapes, peanuts and berries, among other, has shown anti‐proliferative, anti‐estrogenic, and antioxidant properties. We aimed to study the effect of resveratrol on CXCR4‐mediated cell migration. We hypothesize resveratrol will inhibit the ligand‐receptor relation between CXCR4 and CXCL12 decreasing the migration. To accomplish this, we conducted a wound healing assays, in Hs578t breast carcinoma‐cell line and MCF 7 breast adenocarcinoma‐cell lines treated with 25, 50, 100, and 200 μM of resveratrol in the presence of 100 ng/mL of CXCL12. As an internal control we used AMD3100, an antagonist of CXCR4. The results on Hs578t carcinoma cells did not show significant differences in the migration compared to the controls. However, this preliminary data suggest that there is a decrease in migration in the cells treated with 25 and 100 μM of resveratrol, compared to the AMD3100. Regarding MCF‐7 adenocarcinoma cells, we did not observe significant differences in cell migration. Additional experimental replicates are necessary to validate these results. In addition, we are currently studying other malignant and non‐malignant cell lines, including: CCD‐1097 and CCD‐1074 to identify cell specific responses to resveratrol, mediated by the CXCR4‐CXCL12 signaling pathway.Support or Funding InformationNIH‐NIGMS #2R25GM096955This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ras enhances TGF-\u03b2 signaling by decreasing cellular protein levels of its type II receptor negative regulator SPSB1

BackgroundTransformation by oncogene Ras overcomes TGF-β mediated growth inhibition in epithelial cells. However, it cooperates with each other to mediate epithelial to mesenchymal transition (EMT). The mechanism of how these two pathways interact with each other is controversial.MethodsMolecular techniques were used to engineer expression plasmids for Ras, SPRY, TGF-β receptors, type I and II and ubiquitin. Immunoprecipitation and western blots were employed to determine protein-protein interactions, preotein levels, protein phosphorylation while immunofluorecesent staining for molecular co-localization. TGF-β signalling activities is also determined by its luciferase reporter assay. Trans-well assays were used to measure cell migration and invasion.ResultsRas interacts with the SPSB1’s SPRY domain to enhance TGF-β signaling. Ras interacts and colocalizes with the TGF-β type II receptor’s (TβRII) negative regulator SPSB1 on the cell membrane, consequently promoting SPSB1 protein degradation via enhanced mono- and di-ubiquitination. Reduced SPSB1 levels result in the stablization of TβRII, in turn the increase of receptor levels significantly enhance Smad2/3 phosphorylation and signaling. Importantly, forced expression of SPSB1 in Ras transformed cells suppresses TGF-β signaling and its mediated migration and invasion.ConclusionRas positively cooperates with TGF-β signaling by reducing the cellular protein levels of TβRII negative regualtor SPSB1.

AIM2 regulates vascular smooth muscle cell migration in atherosclerosis

BackgroundAtherosclerosis (AS) is a common pathological basis of various cardiovascular and cerebrovascular diseases. Plaque formation is initiated and triggered by vascular smooth musclecells (VSMCs) migration in vascular wall, which gradually aggravates atherosclerosis progression. Absent in melanoma 2 (AIM2), a member of HIN-200 family, plays an important role in activating inflammasome. However, the role of AIM2 in atherosclerotic plaque progression outside of the inflammasome has not yet been reported. MethodsThe potential effect and the underlying mechanism of AIM2 were investigated in apoliporotein E-deficient (ApoE−/−) mice. Murine AIM2 lentivirus, shRNA-AIM2 lentivirus and null lentivirus were constructed and injected intravenously into ApoE−/− mice, which were fed on a high fat diet. The specific mechanism of AIM2 in vascular smooth cells (VSMCs) was explored in vitro. ResultsResults showed the aortic atherosclerotic lesion area was larger with AIM2 over-expression, and the number of smooth muscle cells was enhanced in line with the increased AIM2 levels. AIM2 overexpression also induced the increasing expression of MMP2. In vitro studies revealed that different levels of ox-LDL increased AIM2 expression in a time–dependent manner. Transwell showed that AIM2 mediated migration in VSMCs. The expression of AIM2 can be inhibited when the ROS inhibitor was used. Additionally, the overexpression and inhibition of AIM2 significantly affects HG-induced migration and TGF-β/SMAD signaling pathway in VSMCs. ConclusionThus, we demonstrated that AIM2 could promote the progression of atherosclerotic plaque by increasing migration in VSMCs.

YXQ-EQ Induces Apoptosis and Inhibits Signaling Pathways Important for Metastasis in Non-Small Cell Lung Carcinoma Cells

Background/Aims: Lung cancer is one of the most prevalent malignancies in the world. The 5-year survival rate for non-small cell lung cancer (NSCLC) patients is only approximately 15%, with metastasis as the primary cause of death. This study was aimed to investigate cytotoxic effect of external qi of Yan Xin Qigong (YXQ-EQ) toward human lung adenocarcinoma A549 cells as well as its effect on signaling pathways promoting migration, invasion and epithelial-to-mesenchymal transition (EMT) in A549 cells. Methods: Cytotoxic effect of YXQ-EQ was evaluated using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] and cologenic assays. Apoptosis of treated cells was determined by Annexin V/propidium iodide staining and flow cytometry analysis, while cell migration and invasion were determined using transwell assays and EMT was assessed by morphological changes in cells. Protein expression and phosphorylation were examined by immunoblot analyses. Results: YXQ-EQ induced apoptosis in A549 cells, resulting in a pronounced reduction in viability and clonogenic formation. This was associated with inhibition of phosphorylation of AKT and ERK1/2 and reduced expression of anti-apoptotic proteins BCL-xL, XIAP and survivin. Furthermore, YXQ-EQ inhibited EGF/EGFR signaling and EGF mediated migration and invasion of A549 cells. While TGF-β1 induced phosphorylation of SMAD2/3 and EMT in A549 cells, YXQ-EQ suppressed TGF-β/SMAD signaling and induced cell death in these cells in the presence of TGF-β1. Conclusion: Our findings suggest that YXQ-EQ could exert anti-lung cancer effects via inhibiting signaling pathways that are important for NSCLC cell survival and NSCLC metastasis.

MiR-182 and miR-135b Mediate the Tumorigenesis and Invasiveness of Colorectal Cancer Cells via Targeting ST6GALNAC2 and PI3K/AKT Pathway.

Metastasis is a leading cause of cancer-related death including colorectal cancer (CRC). MicroRNAs are known to regulate cancer pathways and to be expressed aberrantly in cancer. Aberrant sialylation is closely associated with malignant phenotype of tumor cells, including invasiveness and metastasis. This study aimed to investigate the association of miR-182 and miR-135b with proliferation and invasion by targeting sialyltransferase ST6GALNAC2 in CRC cells and explore the potential molecular mechanism. We measured the levels of miR-182, miR-135b, and ST6GALNAC2 in a series of CRC cell lines and tissues using real-time PCR. Bioinformatics analysis and luciferase reporter assay were performed to test the direct binding of miR-182 and miR-135b to the target gene ST6GALNAC2. We also analyzed the possible role of miR-182/-135b on colony formation, wound healing, invasion, and tube formation. The expression of miR-182 and miR-135b was higher in tumor tissues compared to adjacent noncancerous tissues of CRC patients, as well as up-regulated in SW620 cells than in SW480 cells with different metastatic potential. By applying bioinformatics analysis and luciferase reporter assay, we identified ST6GALNAC2 as the direct target of miR-182/-135b. Furthermore, miR-182/-135b inhibited significantly ST6GALNAC2 expression, and consistently, ST6GALNAC2 mediated migration, adhesion, invasion, proliferation, and tumor angiogenesis in CRC cell lines. Additionally, PI3K/AKT signaling pathway was regulated by miR-182/135b, which was partially blocked by altered level of ST6GALNAC2 in CRC. The miR-182/-135b/ST6GALNAC2/PI3K/AKT axis may serve as a predictive biomarker and a potential therapeutic target in CRC treatment.