FGFR3 silencing by siRNA inhibits invasion of A549 cells

Li, Yuhua; Liu, Xiguang; Zhang, Hongjun; Jiang, Tao; Xiao, Wenjing; Zhao, Shufen; Yu, Xiaoyun; Han, Fanjie

doi:10.3892/ol.2016.5278

Cited by 3 publications

(1 citation statement)

References 37 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These proteins are involved in cell proliferation, apoptosis, cell membrane transport, energy metabolism and inflammation‐related responses. (Granja et al, ; Kong et al, ; Li et al, ; Qi et al, ). Furthermore, these findings reveal that the observed proteomic changes are consistent with cytotoxicity results.…”

Section: Discussionmentioning

confidence: 99%

A matrix‐assisted laser desorption ionization–time‐of‐flight–time‐of‐flight–mass spectrometry‐based toxicoproteomic screening method to assess in vitro particle potencies

Ariganello

Das

Breznan

et al. 2018

J of Applied Toxicology

View full text Add to dashboard Cite

Knowledge of biological reactivity and underlying toxicity mechanisms of airborne particulate matter (PM) is central to the characterization of the risk associated with these pollutants. An integrated screening platform consisting of protein profiling of cellular responses and cytotoxic analysis was developed in this study for the estimation of PM potencies. Mouse macrophage (J774A.1) and human lung epithelial cells (A549) were exposed in vitro to Ottawa urban particles (EHC6802) and two reference mineral particles (TiO2 and SiO2). Samples from the in vitro exposure experiment were tested following an integrated classical cytotoxicity/toxicoproteomic assessment approach for cellular viability (CellTiter Blue®, lactate dehydrogenase) and proteomic analyses. Cellular proteins were pre‐fractionated by molecular weight cut‐off filtration, digested enzymatically and were analyzed by matrix‐assisted laser desorption ionization–time‐of‐flight–time‐of‐flight–mass spectrometry for protein profiling and identification. Optimization of detergent removal, pre‐fractionation strategies and enzymatic digestion procedures led to increased tryptic peptide (m/z) signals with reduced sample processing times, for small total protein contents. Proteomic analyses using this optimized procedure identified statistically significant (P < 0.05) PM dose‐dependent changes at the molecular level. Ranking of PM potencies based on toxicoproteomic analysis were in line with classical cytotoxicity potency‐based ranking. The high content toxicoproteomic approach exhibited the potential to add value to risk characterization of environmental PM exposures by complementing and validating existing cytotoxicity testing strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

A matrix‐assisted laser desorption ionization–time‐of‐flight–time‐of‐flight–mass spectrometry‐based toxicoproteomic screening method to assess in vitro particle potencies

Ariganello

Das

Breznan

et al. 2018

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

Regulatory mechanism of the Glabrene against non‐small cell lung cancer by suppressing FGFR3

He,

Wu,

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

BackgroundNon‐small cell lung cancer (NSCLC) is a highly malignant tumor with limited effective treatment options. This study aimed to investigate the regulatory mechanism of Glabrene on NSCLC through its interaction with FGFR3.MethodsHCC827 cells were implanted into nude mice and treated with Glabrene. Tumor volume was monitored at 0, 3, 6, and 9 days after medical treatment. Tissue analysis included Hematoxylin and Eosin (HE) and Terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP Nick End Labeling (TUNEL) staining, as well as immunohistochemistry for Ki67, ERK1/2, and p‐ERK1/2 expression. Cell viability was determined with the CCK8 method. We utilized immunofluorescence techniques to observe apoptosis, as well as the levels of E‐cadherin and Vimentin expression. Cellular proliferation was determined via plate cloning assay and cellular mobility was determined via scratch assay. Cellular invasion ability was assessed via a transwell assay. mRNA and protein levels of FGFR3, MMP1, MMP9, vimentin, E‐cadherin, ERK1/2, and p‐ERK1/2 were detected via qPCR and Western blot. IGF‐1, VEGF, and Estradiol (E2) levels were measured through Enzyme linked immunosorbent assay (ELISA).ResultsThis study verified that Glabrene was capable of suppressing tumor growth in NSCLC mice, reversing tumor tissue's pathological morphology, attenuating the capacities of cancerous cells' proliferation, migration, and invasion, and leading to apoptosis. Besides, Glabrene could reduce the FGFR3 expression in HCC827 cells. Over‐expression of FGFR3 promotes the proliferation of HCC827 cells, increase both contents of IGF‐1, VEGF, and E2, and expressions of MMP1, MMP9, vimentin, and p‐ERK1/2, while Glabrene inhibited FGFR3. Glabrene, and inhibition of FGFR3 expression were capable of decreasing FGFR3, MMP1, MMP9, vimentin, and p‐ERK1/2 expression, as well as contents of IGF‐1, VEGF, and E2 in model mice and HCC827 cells, and promoting the expression of E‐cadherin.ConclusionGlabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1/2 phosphorylation and suppression of epithelial‐mesenchymal transition (EMT).

show abstract

Targeting FGFR3 is a Useful Therapeutic Strategy for Rheumatoid Arthritis Treatment

Yu,

Cheng,

Huang

et al. 2023

CMP

View full text Add to dashboard Cite

background: Rheumatoid arthritis (RA) is a systemic inﬂammatory disease in which TNF-α plays an important role. Fibroblast growth factor receptor 3 (FGFR3) is reportedly involved in RA by regulating expression of inﬂammatory cytokines. objective: This study examined the expression profile of FGFR3 in human synovial biopsy tissues and evaluated its gene silencing effects on behaviors of synovial cells. method: Immunohistochemical staining was used to measure FGFR3 expression in human RA joint tissues. Cell proliferation, migration, and apoptosis assays were used to monitor behavioral changes in cultured synovial SW-982 cells with siRNA-mediated FGFR3 gene silencing. Immunofluorescent staining and western blotting were used to detect molecular changes in the FGFR3 gene silenced cells. result: FGFR3 up-regulation was noted in both cytoplasms and nuclei of synovial cells in human RA joints. FGFR3 siRNA delivery experiments corroborated that FGFR3 knockdown decreased proliferation and migration, and triggered apoptosis of synovial cells. The FGFR3 gene knockdown enhanced constitutive expression of epithelial marker E-cadherin and conversely suppressed expression of epithelial-mesenchymal transition (EMT) markers, including Snail, fibronectin and vimentin. In addition, FGFR3 silencing significantly reduced the constitutive expressions of TNF-α, transcription factor NF-kB, and downstream COX-2 protein and collagenolytic enzyme MMP-9. MAPK inhibition markedly suppressed constitutive levels of NF-kB, COX-2 and MMP-9. conclusion: Genetic interference of FGFR3 could modulate the expression of inflammatory mediators and EMT markers in the synovial cells. Targeting FGFR3/MAPK signal axis may be considered as a useful therapeutic strategy to ameliorate the development of RA.

show abstract

FGFR3 silencing by siRNA inhibits invasion of A549 cells

Cited by 3 publications

References 37 publications

A matrix‐assisted laser desorption ionization–time‐of‐flight–time‐of‐flight–mass spectrometry‐based toxicoproteomic screening method to assess in vitro particle potencies

A matrix‐assisted laser desorption ionization–time‐of‐flight–time‐of‐flight–mass spectrometry‐based toxicoproteomic screening method to assess in vitro particle potencies

Regulatory mechanism of the Glabrene against non‐small cell lung cancer by suppressing FGFR3

Targeting FGFR3 is a Useful Therapeutic Strategy for Rheumatoid Arthritis Treatment

Contact Info

Product

Resources

About