P68.04 Molecular Mechanism of MK2 Promoting Lung Adenocarcinoma Progression by Phosphorylating Transcription Regulator CRABP2

2021 ◽  
Vol 16 (10) ◽  
pp. S1200-S1201
Author(s):  
J. Deng ◽  
J. Xu ◽  
F. Zhong ◽  
J. Tang ◽  
K. Fang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Molecular Mechanism ◽  
Transcription Regulator

scholarly journals Fbxw7 and Skp2 Regulate Stem Cell Switch between Quiescence and Mitotic Division in Lung Adenocarcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Wenzhu Zhang ◽  
Zihan Ren ◽  
Lanling Jia ◽  
Xin Li ◽  
Xinshan Jia ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanism ◽  
Nuclear Translocation ◽  
A549 Cells ◽  
Mitotic Division ◽  
S Phase ◽  
G1 Phase ◽  
Skp2 Expression ◽  
Xenograft Models

Background/Aims. The molecular mechanism of dormancy initiation of cancer stem cells (CSCs) is not clear. This study was to explore the molecular mechanism by which CSCs switch from mitotic division to quiescence. Methods. MTT assays, flow cytometry, Western blotting, qRT-PCR, and immunofluorescence staining were used to test cell viability, cell cycle and expression of F-box and WD repeat domain-containing 7 (Fbxw7), c-myc, S phase kinase associated protein-2 (Skp2), cyclin-dependent kinase inhibitor 1B (p27), octamer-binding transcription factor 3/4 (Oct3/4), and β catenin gene in 5-fluorouracil (5-FU)-treated A549 cells. Lung adenocarcinoma xenograft models were employed to detect the effects of Fbxw7 on tumor growth. Results. 5-FU inhibited the proliferation of A549 cells, with a median inhibitory concentration (IC50) of 200 μg/ml after 24 h treatment. 5-FU treatment increased the expressions of Oct3/4, Fbxw7, and p27 and increased the number of A549 cells at G0/G1. 5-FU treatment triggered nuclear translocation of β-catenin, decreased the expression levels of c-myc and Skp2, and decreased the number of A549 cells at S phase. Release from 5-FU decreased the expressions of Oct3/4, Fbxw7 and p27; decreased the percentage of cells in the G0/G1 phase; increased the expressions of Skp2 and c-myc; and increased the proportion of cells in S phase. 5-FU treatment led to high expressions of Oct3/4, c-myc, and p27, with low expressions of Fbxw7 and Skp2. Knockdown of Fbxw7 augmented the expression of c-myc and decreased the proportion of A549 cells in Go/G1 phase. Skp2 siRNA increased the expression of p27 and the percentage of G0/G1 phase cells and reduced the proportion of S phase cells. Fbxw7 overexpression inhibited tumor growth in mouse lung adenocarcinoma xenograft models. When Fbxw7 expression was low, Skp2 expression was higher in lung adenocarcinoma tissues and associated with the differentiation of lung adenocarcinoma. Conclusion. 5-FU enriches the CSCs in lung adenocarcinoma cells via increasing Fbxw7 and decreasing Skp2 expression, followed by downregulation of c-myc and upregulation of p27, which switches cells to quiescence.

scholarly journals P2.14-06 The Study of Rac3 Molecular Mechanism Through ERK Signaling Pathway in Lung Adenocarcinoma

2019 ◽  
Vol 14 (10) ◽  
pp. S831
Author(s):  
J. Li ◽  
H. Sun ◽  
G. Wang ◽  
C. Zhang ◽  
Y. Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Erk Signaling

scholarly journals Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nan Gao ◽  
Baoguo Ye
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Biological Function ◽  
Wnt Signaling Pathway ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Lung adenocarcinoma (LUAD), a widespread histopathological subtype of lung cancer, is deemed as a malignant tumor with a peak risk of mortality. Emerged as RNA with a loop structure that depleted protein coding ability, circular RNA (circRNA) has been identified as a regulator in cancer progression. Circ-SOX4, identified as a novel circRNA, has not been studied in any cancer yet. Thus, the regulatory function that circ-SOX4 exerts on LUAD development remains obscure. Aim of the study This study aimed to investigate the biological function and molecular mechanism of circ-SOX4 in LUAD. Methods The expression of circ-SOX4 was detected by qRT-PCR. CCK-8, colony formation, transwell and wound healing assays were performed to explore the biological function of circ-SOX4 in LUAD. The interaction between miR-1270 and circ-SOX41 (or PLAGL2) was confirmed by RNA pull down, luciferase reporter and RIP assays. Results Circ-SOX4 was found to be obviously upregulated in LUAD tissues and cells, and knockdown of it inhibited cell proliferation, invasion and migration in LUAD. Furthermore, silenced circ-SOX4 also inhibited LUAD tumor growth. Molecular mechanism assays revealed that circ-SOX4 interacted with miR-1270 in LUAD. Besides, PLAGL2 was confirmed as a downstream gene of miR-1270. Rescue assays validated that miR-1270 suppression or PLAGL2 overexpression countervailed circ-SOX4 depletion-mediated inhibition on cell proliferation, invasion and migration in LUAD. Additionally, it was discovered that circ-SOX4/miR-1270/PLAGL2 axis activated WNT signaling pathway in LUAD. Conclusions Circ-SOX4 boosted the development of LUAD and activate WNT signaling pathway through sponging miR-1270 and modulating PLAGL2, which provided a valuable theoretical basis for exploring underlying therapeutic target in LUAD.

scholarly journals Santamarine Inhibits NF-κB Activation and Induces Mitochondrial Apoptosis in A549 Lung Adenocarcinoma Cells via Oxidative Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xuefeng Wu ◽  
Hua Zhu ◽  
Jingzhe Yan ◽  
Muhammad Khan ◽  
Xiuyan Yu
Keyword(s):  
Oxidative Stress ◽  
Lung Adenocarcinoma ◽  
Anticancer Activity ◽  
Molecular Mechanism ◽  
Dependent Manner ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
A549 Lung

Santamarine (STM), a sesquiterpene lactone component of Magnolia grandiflora and Ambrosia confertiflora, has been shown to possess antimicrobial, antifungal, antibacterial, anti-inflammatory, and anticancer activities. However, no study has yet been conducted to investigate the molecular mechanism of STM-mediated anticancer activity. In the present study, we found that STM inhibits growth and induces apoptosis in A549 lung adenocarcinoma cells through induction of oxidative stress. STM induces oxidative stress by promoting reactive oxygen species (ROS) generation, depleting intracellular glutathione (GSH), and inhibiting thioredoxin reductase (TrxR) activity in a dose-dependent manner. Further mechanistic study demonstrated that STM induces apoptosis by modulation of Bax/Bcl-2 expressions, disruption of mitochondrial membrane potential, activation of caspase-3, and cleavage of PARP in a dose-dependent manner. Moreover, STM inhibited the constitutive and inducible translocation of NF-κBp65 into the nucleus. IKK-16 (I-κB kinase inhibitor) augmented the STM-induced apoptosis, indicating that STM induces apoptosis in A549 cells at least in part through NF-κB inhibition. Finally, STM-induced apoptosis and expressions of apoptosis regulators were effectively inhibited by thiol antioxidant N-acetyl-L-cysteine (NAC), indicating that STM exerts its anticancer effects mainly through oxidative stress. To the best of our knowledge, this is the first report providing evidence of anticancer activity and molecular mechanism of STM.

scholarly journals RBM10 Interacts with CTBNNBIP1 and Represses Lung Adenocarcinoma Progression Through the Wnt/β- catenin Pathway

2021 ◽  
Author(s):  
Yingyue Cao ◽  
Xin Wang ◽  
Qingwei Meng ◽  
Jianxiong Geng ◽  
Shanqi Xu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Molecular Mechanism ◽  
Rna Binding ◽  
Bioinformatics Analysis ◽  
Protein Extraction ◽  
Binding Motif ◽  
Loss Of Function ◽  
Mesenchymal Transition

Abstract Background: RNA-binding motif protein 10 (RBM10), one of the RNA-binding protein (RBP) family, has a tumor suppressor role in various tumors. However, the functional role of RBM10 in lung adenocarcinoma (LUAD) and the molecular mechanism remain unclear. The aim of this study was to explore the effect of RBM10 on LUAD growth and metastasis and its molecular mechanism.Methods: Bioinformatics analysis was used to predict RBM10 expression and its associations with clinicopathological features and prognosis in LUAD. Gain- and loss- of function experiments were conducted to investigate the biological functions of RBM10 both in vitro and in vivo. RNA-seq, bioinformatics programs, western blot, qRT-PCR, TOP/FOP flash reporter, co-immunoprecipitation (co-IP), nuclear and cytoplasmic protein extraction and rescue experiments were used to reveal the underlying mechanisms.Results: Bioinformatics analysis showed that RBM10 was significantly downregulated and closely correlated with poor prognosis in LUAD patients. RBM10 silencing significantly promoted the LUAD proliferation, migration, invasion ability, while RBM10 overexpression had the opposite effects. Furthermore, upregulation of RBM10 inhibited growth and metastasis of LUAD in vivo. Additionally, RBM10 suppressed tumor progression through inhibiting epithelial to mesenchymal transition (EMT) in LUAD cells. Mechanistically, RBM10 interacts with β-catenin interacting protein 1 (CTNNBIP1) and positively regulates its expression, thus inactivating the Wnt/β-catenin pathway. Conclusions: This is the first study that reported how RBM10 suppresses cell proliferation and metastasis of LUAD by negatively regulating the Wnt/β-catenin pathway through interaction with CTNNBIP1. These data suggest that RBM10 may be a promising new target or clinical biomarker for LUAD therapy.

scholarly journals TGIF2 promotes the progression of lung adenocarcinoma by bridging EGFR/RAS/ERK signaling to cancer cell stemness

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Renle Du ◽  
Wenzhi Shen ◽  
Yi Liu ◽  
Wenjuan Gao ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Fate ◽  
Lung Metastases ◽  
Erk Signaling ◽  
Egfr Signaling ◽  
Aberrant Expression ◽  
Cell Fate Decisions ◽  
Transcription Regulator ◽  
Node Metastasis

AbstractTGF-β-induced factor homeobox 2 (TGIF2) is a transcription regulator that plays essential roles in the regulation of development and cell fate decisions. Aberrant expression of TGIF family proteins has been observed in several cancers, including ovarian, esophageal, and colorectal cancers. Here, we report that TGIF2 mediates the EGFR–RAS–ERK signaling pathway to enhance the stemness of lung adenocarcinoma (LUAD) cells and, therefore, promote the progression and metastasis of LUAD. We found that high TGIF2 expression was closely correlated with tumor growth, lymph node metastasis, and survival of patients with LUAD. Mice bearing TGIF2-silenced H1299 xenografts developed smaller tumors and fewer lung metastases. Importantly, silencing TGIF2 decreased the cancer stem cell (CSC)-like properties in A549 and H1299 cells. Furthermore, we identified that TGIF2 binding to the OCT4 promoter promotes its expression. In both LUAD cells and in vivo LUAD mouse models, we revealed that EGFR–RAS–ERK signaling phosphorylated TGIF2 and increased its stability, which was important for TGIF2-promoted LUAD stemness since phosphorylation-deficient TGIF2 mutants lost these functions. Thus, our study revealed that an important factor, TGIF2, bridges EGFR signaling to the CSC characteristics of LUAD cells, which can be utilized as an effective target for LUAD therapy.

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