PARK7/DJ-1 inhibition decreases invasion and proliferation of uveal melanoma cells

2021 ◽  
pp. 030089162110617
Author(s):  
Nerea Lago-Baameiro ◽  
Maria Santiago-Varela ◽  
Tamara Camino ◽  
Paula Silva-Rodríguez ◽  
Manuel Bande ◽  
...  
Keyword(s):  
Real Time ◽  
Uveal Melanoma ◽  
Metastatic Cells ◽  
Phosphorylated Akt ◽  
Negative Effect ◽  
And Migration ◽  
Cell Migration And Proliferation ◽  
Cell Analyzer ◽  
Proliferation And Invasion

Introduction: PARK7/DJ-1 is an oncogene that is associated with tumorigenesis in many cancers. Recent studies have demonstrated the importance of DJ-1 in the origin and development of uveal melanoma (UM). We present an analysis of the role of the DJ-1 protein in UM cells, especially in its effect on proliferation and migration. Methods: UM cells from a primary tumor, Mel 270, and its liver metastasis, OMM2.5, were transfected with lentiviral-delivered shRNA against PARK7/DJ-1. Evaluation of cell migration and proliferation was performed using the xCELLigence real-time cell analyzer (RTCA). The effect of DJ-1 inhibition on the PTEN-Akt signaling pathway was also studied by immunoblotting. Results: The silencing of PARK7/DJ-1 oncoprotein expression produced a significant decrease of phosphorylated Akt (S473) in Mel270 and in metastatic OMM2.5 UM cells with no alteration on tumor suppressor PTEN expression. The diminution of PARK7/DJ-1 expression significantly inhibited real-time proliferation and invasion of Mel270 and OMM2.5 and the invasion potential of the metastatic cells. Conclusion: DJ-1 appears to play a key role on the PTEN/Akt pathway in UM. DJ-1 inhibition appears to have a negative effect on proliferation and invasion of UM cells. This suggests DJ-1 as a potential therapeutic target in UM.

scholarly journals The Role of HGF/MET Signaling in Metastatic Uveal Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5457
Author(s):  
Ryota Tanaka ◽  
Mizue Terai ◽  
Eric Londin ◽  
Takami Sato
Keyword(s):  
Uveal Melanoma ◽  
Treatment Resistance ◽  
Therapeutic Benefit ◽  
Cellular Functions ◽  
Major Mechanism ◽  
Pathway Activation ◽  
Mesenchymal Epithelial Transition Factor ◽  
And Migration ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling promotes tumorigenesis and tumor progression in various types of cancer, including uveal melanoma (UM). The roles of HGF/MET signaling have been studied in cell survival, proliferation, cell motility, and migration. Furthermore, HGF/MET signaling has emerged as a critical player not only in the tumor itself but also in the tumor microenvironment. Expression of MET is frequently observed in metastatic uveal melanoma and is associated with poor prognosis. It has been reported that HGF/MET signaling pathway activation is the major mechanism of treatment resistance in metastatic UM (MUM). To achieve maximal therapeutic benefit in MUM patients, it is important to understand how MET signaling drives cellular functions in uveal melanoma cells. Here, we review the HGF/MET signaling biology and the role of HGF/MET blockades in uveal melanoma.

scholarly journals Knockdown of SLC34A2 Inhibits Hepatocellular Carcinoma Cell Proliferation and Invasion

2016 ◽  
Vol 24 (6) ◽  
pp. 511-519 ◽  
Author(s):  
Yanhua Li ◽  
Xia Chen ◽  
Hong Lu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Mesenchymal Transition ◽  
Human Carcinomas ◽  
And Migration ◽  
Proliferation And Invasion ◽  
Hcc Cells

The gene solute carrier family 34 (sodium phosphate), member 2 (SLC34A2), is a member of the SLC34 family. Increasing evidence suggests that SLC34A2 is involved in the development of many human carcinomas. However, its role in hepatocellular carcinoma (HCC) is still unclear. Therefore, in this study we investigated the role of SLC34A2 in HCC and explored the underlying mechanism. We found that the expression of SLC34A2 is upregulated in HCC cell lines. Knockdown of SLC34A2 obviously inhibited HCC cell proliferation, migration/invasion, and the epithelial‐mesenchymal transition (EMT) phenotype. Furthermore, knockdown of SLC34A2 significantly inhibited the expression of phosphorylated PI3K and AKT in HCC cells. Taken together, these results suggest that knockdown of SLC34A2 inhibits proliferation and migration by suppressing activation of the PI3K/AKT signaling pathway in HCC cells, and SLC34A2 may be a potential therapeutic target for the treatment of HCC.

scholarly journals Downregulated MiR-206 expression promotes the proliferation and migration of macrophages by regulating IL-17A/REG3A pathway

2020 ◽  
Vol 18 ◽  
pp. 205873922091749
Author(s):  
Xuan Huang ◽  
Fang Gong ◽  
Zhixian Lu ◽  
Jie Zhu ◽  
Qun Yu
Keyword(s):  
Pcr Analysis ◽  
Chain Reaction ◽  
Inflammatory Infiltration ◽  
Interleukin 17A ◽  
Polymerase Chain ◽  
And Migration ◽  
Cell Migration And Proliferation ◽  
Migration Of Macrophages ◽  
Proliferation And Migration

This study sought to investigate the role of miR-206 in polymyositis/dermatomyositis (PM/DM) development. Transwell and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay were performed to investigate cell migration and proliferation. Real-time polymerase chain reaction (PCR) analysis was used to determine the expression of miR-206, interleukin-17A (IL-17A), IL-17 receptor A (IL-17RA), and regenerating islet-derived protein 3-alpha (REG3A). Significantly, miR-206 mimics decreased macrophage migration and proliferation, while miR-206 inhibitors exhibited the opposite effects. Indeed, elevating IL-17RA levels resulted in increased REG3A expression, which was inhibited by IL-17RA siRNA. Besides, miR-206 mimics decreased IL-17A and REG3A expressions, but miR-206 inhibitors showed opposite effects. Moreover, miR-206 expression in PM/DM patients was significantly reduced compared with the healthy controls, while IL-17A and REG3A expressions substantially increased among PM/DM patients. These findings suggested that downregulation of miR-206 increased the migration and proliferation of macrophages via IL-17A/REG3A signaling pathway, which could promote the inflammatory infiltration in PM/DM.

scholarly journals Effect of Lentivirus-Mediated miR-499a-3p on Human Umbilical Vein Endothelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Huilei Zheng ◽  
Juan Li ◽  
Ying Chen ◽  
Danping Gong ◽  
Jianlin Wen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Polymerase Chain ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells ◽  
Cell Migration And Proliferation ◽  
Scratch Tests ◽  
Proliferation And Migration

Objective. To explore the possible role of miR-499a-3p in the function of primary human umbilical vein endothelial cells (HUVECs) and the expression of ADAM10 in primary HUVEC. Method. miR-499a-3p was first transfected into primary HUVECs via lentivirus vector. The viability, proliferation, and migration of stable transfected primary HUVEC were then determined by flow cytometry, CCK8 assays, scratch tests, and Transwell tests. The transcription of miR-499a-3p and ADAM10 was examined by reverse transcription-polymerase chain reaction (RT-PCR), and the expression of ADAM10 was examined by Western blot (WB). Results. After transfection, miR-499a-3p transcription was significantly increased (P<0.01), compared to the blank and nonspecific control (NC) groups, while both ADAM10 transcription and expression were significantly decreased (P<0.05). In contrast, in the inhibitors group, miR-499a-3p transcription was significantly reduced (P<0.05) whereas both ADAM10 transcription and expression were significantly increased (P<0.05). The viability, proliferation, and migration of primary HUVECs were significantly impaired (P<0.05) by the transfection of miR-499a-3p but enhanced by miR-499a-3p inhibitors (P<0.05). Conclusions. Upregulation of miR-499a-3p transcription will inhibit the expression of ADAM10 in HUVECs; cell migration and proliferation, however, promote apoptosis. And reverse effects were established by downregulation of miR-499a-3p transcription. All these effects may be achieved by regulating the transcription and expression of ADAM10. These results combined suggested that miR-499a-3p may affect the proliferation, migration, and apoptosis of endothelial cells and regulate AS by regulating ADAM10. miR-499a-3p may become a candidate biomarker for the diagnosis of unstable angina pectoris (UA).

scholarly journals Chloride Accumulation Drives Volume Dynamics Underlying Cell Proliferation and Migration

2009 ◽  
Vol 101 (2) ◽  
pp. 750-757 ◽  
Author(s):  
Christa W. Habela ◽  
Nola Jean Ernest ◽  
Amanda F. Swindall ◽  
Harald Sontheimer
Keyword(s):  
Cell Volume ◽  
Glioma Cells ◽  
Volume Changes ◽  
Dividing Cells ◽  
Chloride Accumulation ◽  
And Migration ◽  
Cell Migration And Proliferation ◽  
Immature Cells ◽  
New Framework

During brain development, progenitor cells migrate over long distances through narrow and tortuous extracellular spaces posing significant demands on the cell's ability to alter cell volume. This phenotype is recapitulated in primary brain tumors. We demonstrate here that volume changes occurring spontaneously in these cells are mediated by the flux of Cl− along with obligated water across the cell membrane. To do so, glioma cells accumulate Cl− to ∼100 mM, a concentration threefold greater than predicted by the Nernst equation. Shunting this gradient through the sustained opening of exogenously expressed GABA-gated Cl− channels caused a 33% decrease in cell volume and impaired the ability of cells to migrate in a spatially constrained environment. Further, dividing cells condense their cytoplasm prior to mitosis, a phenomenon which is associated with the release of intracellular Cl− as indicated by a 40-mM decrease in [Cl−]i. These findings provide a new framework for considering the role of intracellular Cl− in glioma cells. Here, Cl− serves as an important osmotically active regulator of cell volume being the energetic driving force for volume changes required by immature cells in cell migration and proliferation. This mechanism that was studied in CNS malignancies may be shared with other immature cells in the brain as well.

scholarly journals CSIG-05. TRPM7 INDUCES MECHANISTIC TARGET OF Rap1b THROUGH DOWNREGULATION OF miR-28-5p IN GLIOMA PROLIFERATION AND INVASION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi44-vi45
Author(s):  
Jingwei Wan ◽  
Alyssa Guo ◽  
Mingli Liu
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Kinase Domain ◽  
Glioma Cell Proliferation ◽  
And Migration ◽  
Proliferation And Invasion

Abstract Our previous findings demonstrate that TRPM7 is critical in regulating human glioma tumorigenesis. miRNA participate in complex regulatory networks that may affect almost every cellular and molecular processes in glioma formation and progression, because a specific miRNA may simultaneously regulate many targets; While, a single protein target can be regulated by different miRNAs. Here, we explored the role of miRNAs in the progression of human gliomas by comparing miRNA expression profiles due to differentially expressed TRPM7. We determined 1) miRNA targets of TRPM7 by miroRNA microarray analysis upon TRPM7 silencing in glioma cell lines. 2) whether TRPM7 regulates glioma cell proliferation (MTT) and migration/invasion (transwell invasion assay) through different functional domains by transfecting wild-type human TRPM7 (wtTRPM7) or constructs with the α-kinase domain deleted (Δkinase) or with a point mutation within the ATP binding site of the α-kinase domain (K1648R-KR) into glioma cells. 3) the roles of miR-28-5p in glioma tumorigenesis by over- or under-expressing miR-28-5p in vitro. 4) whether Rap1b is a target of miR28-5p and the role of Rap1b in glioma tumorigenesis. 5) whether Rap1b can counteract the miR28-5p function on glioma tumorigenesis. We found 1) a list of 16 downregulated and 10 upregulated miRNAs that are statistically significant with fold changes greater than 2 by TRPM7 knock-down by miRNA microarray, and miR-28-5p as a promising candidate for functional analyses. 2) cell invasion was significantly reduced in Δkinase or K1648R transfectants, indicating that TRPM7 kinase activity is required for glioma cell migration/invasion. 3) overexpression of miR-28-5p caused a significant decrease in cell proliferation and migration by targeting Rap1b. 4) Co-transfection with siRap1b with miR28-5p inhibitor reduced the glioma cell proliferation and invasion caused by the latter. In summary, TRPM7 induces mechanistic target of Rap1b through downregulation of miR-28-5p in glioma proliferation and invasion.

scholarly journals EGFR transcriptionally upregulates UTX via STAT3 in non-small cell lung cancer

2021 ◽  
Author(s):  
Lin Zhou ◽  
Xiaomu Wang ◽  
Jingya Lu ◽  
Xiangning Fu ◽  
Yangkai Li
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Real Time ◽  
Quantitative Pcr ◽  
Small Cell ◽  
Small Cell Lung ◽  
Real Time Quantitative Pcr ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Histone demethylase UTX has been reported to participate in the occurrence and development of many cancers in tissue-specific manners. However, the role of UTX in non-small cell lung cancer (NSCLC) and exactly what regulates the expression of UTX remains unclear. Here, we analyzed the role of UTX in NSCLC in association with the widely recognized tumor driver epidermal growth factor receptor (EGFR). Methods UTX levels in clinical samples were detected by immunohistochemistry staining, western blotting and real-time quantitative PCR. The expression of UTX in tumor tissue was correlated with the phosphorylation of EGFR. Cell proliferation and migration were evaluated by MTT and wound-healing assays. The impact of EGFR and its downstream pathways on UTX was explored with corresponding inhibitors, and examined by western blotting and real-time quantitative PCR. Results In this study, we found that the expression of UTX in cancer tissues of patients with NSCLC was significantly higher than that in paracancerous tissues, and positively associated with EGFR phosphorylation levels. In addition, in NSCLC cell lines, UTX can promote proliferation and migration, while inhibition of its enzyme activity suppressed cell growth. Moreover, UTX expression was significantly upregulated when EGFR signaling pathway was activated, and vice versa when EGFR pathway was inhibited by tyrosine kinase inhibitor. Further mechanistic studies suggested that the activation of EGFR activated its downstream JAK/STAT3 signaling pathway and promoted STAT3 phosphorylation; the phosphorylated STAT3 transcriptionally promoted the levels of UTX. Conclusions These results suggest an “EGFR-STAT3-UTX” axis that plays an oncogenic role in NSCLC.

scholarly journals Dynamic assessment of cell viability, proliferation and migration using real time cell analyzer system (RTCA)

2014 ◽  
Vol 67 (2) ◽  
pp. 379-386 ◽  
Author(s):  
Mani Roshan Moniri ◽  
Ada Young ◽  
Kelsey Reinheimer ◽  
Jarrett Rayat ◽  
Long-Jun Dai ◽  
...  
Keyword(s):  
Cell Viability ◽  
Real Time ◽  
Dynamic Assessment ◽  
And Migration ◽  
Cell Analyzer ◽  
Proliferation And Migration

Social Motives Predict Loneliness During a Developmental Transition

2017 ◽  
Vol 76 (4) ◽  
pp. 145-153 ◽  
Author(s):  
Jana Nikitin ◽  
Alexandra M. Freund
Keyword(s):  
Social Relationships ◽  
Well Being ◽  
Social Avoidance ◽  
Social Approach ◽  
Social Motives ◽  
Developmental Transitions ◽  
Avoidance Motivation ◽  
Negative Effect ◽  
Low Levels

Abstract. Establishing new social relationships is important for mastering developmental transitions in young adulthood. In a 2-year longitudinal study with four measurement occasions (T1: n = 245, T2: n = 96, T3: n = 103, T4: n = 85), we investigated the role of social motives in college students’ mastery of the transition of moving out of the parental home, using loneliness as an indicator of poor adjustment to the transition. Students with strong social approach motivation reported stable and low levels of loneliness. In contrast, students with strong social avoidance motivation reported high levels of loneliness. However, this effect dissipated relatively quickly as most of the young adults adapted to the transition over a period of several weeks. The present study also provides evidence for an interaction between social approach and social avoidance motives: Social approach motives buffered the negative effect on social well-being of social avoidance motives. These results illustrate the importance of social approach and social avoidance motives and their interplay during developmental transitions.

Credit constraints and Rural Migration: Evidence from Six Villages in Uttar Pradesh

2018 ◽  
Vol 15 (3) ◽  
pp. 389-398
Author(s):  
Ruchi Singh
Keyword(s):  
Credit Constraints ◽  
Uttar Pradesh ◽  
Binary Logistic Regression ◽  
Binary Logistic Regression Model ◽  
Male Migration ◽  
Rural Economies ◽  
And Migration ◽  
The Relationship ◽  
The Empirical Analysis

Rural economies in developing countries are often characterized by credit constraints. Although few attempts have been made to understand the trends and patterns of male out-migration from Uttar Pradesh (UP), there is dearth of literature on the linkage between credit accessibility and male migration in rural Uttar Pradesh. The present study tries to fill this gap. The objective of this study is to assess the role of credit accessibility in determining rural male migration. A primary survey of 370 households was conducted in six villages of Jaunpur district in Uttar Pradesh. Simple statistical tools and a binary logistic regression model were used for analyzing the data. The result of the empirical analysis shows that various sources of credit and accessibility to them play a very important role in male migration in rural Uttar Pradesh. The study also found that the relationship between credit constraints and migration varies across various social groups in UP.

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