scholarly journals EGFL6 Promotes Bone Metastasis of Lung Adenocarcinoma by Enhancing Osteoclast Differentiation and Stimulating Cancer Cell Metastasis

2022 ◽  
Author(s):  
Xiaoting Song ◽  
Xu Cheng ◽  
Xiangang Jin ◽  
Shengyu Ruan ◽  
Xianquan Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Bone Resorption ◽  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
Osteoclast Differentiation ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Mesenchymal Transformation

Abstract Background Lung cancer is still the most fatal cancer today with approximately 30%-40% of these patients will develop bone metastasis. Lung adenocarcinoma (LUAD) is the most common and aggressive type of lung cancer. The relationship between LUAD and bone metastasis and its underlying mechanism remains unclear. This study proved that epidermal growth factor-like domain multiple 6 (EGFL6) was highly expressed in LUAD specimens of patients, and the expression level was positively correlated with bone metastasis of LUAD. Method The expression of EGFL6 in cancer tissues was detected by IHC. CCK-8, colony formation assay, migration and invasion assay, wound healing assay, immunocytochemistry, RT-PCR, Western blotting, ELISA, bone resorption, TRAP staining and H&E staining were performed. A nude mouse model of LUAD-induced bone destruction was established by injecting A549 cells in different EGFL6 expression levels. Results EGFL6 is elevated in LUAD and is associated with bone metastasis. In vivo, implantation of human adenocarcinoma A549 cells with a higher expression of EGFL6 not only increased tumor growth rate but also bone resorption of tibias in nude mice. In vitro, the secretion of EGFL6 from A549 cells increased osteoclast differentiation but had little effect on osteogenic differentiation. To reveal the underlying mechanism, we demonstrated that EGFL6 enhanced osteoclast differentiation through activating nuclear factor-kappa B (NF-κB) and downstream c-Fos/NFATc1 signaling pathways, and in addition promoted the proliferation, migration and invasion of A549 cells through enhancing the epithelial mesenchymal transformation (EMT) and promoting Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways. Conclusions We unveil EGFL6 as a predictor in bone metastasis of LUAD and underscore the relevance of EGFL6 as a therapeutic target.

scholarly journals Low expression of miR-192 in NSCLC and its tumor suppressor functions in metastasis via targeting ZEB2

2016 ◽  
Vol 11 (1) ◽  
pp. 293-297 ◽  
Author(s):  
Zhang Yunxia ◽  
Dong Hongying
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Real Time ◽  
Real Time Pcr ◽  
Ectopic Expression ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Invasion Assays

AbstractObjectivesLung cancer is the leading cause of cancer-related death, with non-small cell lung cancer (NSCLC) accounting for more than 80% of all lung cancer cases. The aim of this study was to investigate the function and underlying mechanism of microRNA-192 (miR-192) in metastasis of NSCLC cells.MethodsReal-time PCR was applied to quantify the expression of miR-192 in NSCLC tissues and cell lines, matched with their corresponding controls. The biological roles of miR-192 were studied in NSCLC cells using the wound healing and trans well invasion assays. Real-time PCR and western blot were used to evaluate the regulation of ZEB2 by miR- 192.ResultsMiR-192 was expressed significantly lower in NSCLC tissues/cells when compared with controls. Ectopic expression of miR-192 strongly inhibited cell migration and invasion in NSCLC A549 cells. Further investigation revealed ZEB2, an EMT regulator, was one of the downstream targets regulated by miR-192.ConclusionThese results suggested that miR-192 inhibits the metastasis of NSCLC cells by targeting ZEB2, and thus is an important tumor suppressor.

scholarly journals The Potential Roles of Exosomal miR-214 in Bone Metastasis of Lung Adenocarcinoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Jian Zhang ◽  
Jiangmei Wu
Keyword(s):  
Bone Metastasis ◽  
Bone Resorption ◽  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Osteoclast Differentiation ◽  
Peripheral Circulation ◽  
Bone Homeostasis ◽  
Bone Microenvironment ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Bone metastasis is closely related to the alterations of bone microenvironment. In this article, we hypothesize that exosomes may be involved in the “vicious circle” by transferring miR-214. miR-214 is highly expressed in lung adenocarcinoma, and is closely related to the degree of lung cancer progression. As a key regulator of bone homeostasis, miR-214 promotes osteoclast differentiation and mediates intercellular communication between osteoclasts and osteoblasts via the way of exosomal miRNA. Therefore, it is highly probable that exosomal miR-214 derived from lung adenocarcinoma may disrupt bone homeostasis by enhancing bone resorption. Exosomal miR-214 can be released by lung adenocarcinoma cells, enters peripheral circulation, and is taken up by osteoclasts, consequently stimulating osteoclast differentiation. The enhanced bone resorption alters the bone microenvironment by releasing multiple cytokines and growth factors favoring cancer cells. The circulating cancer cells migrate to bone, proliferate, and colonize, resulting in the formation of metastasis. Furthermore, osteoclasts derived exosomal miR-214 may in turn contribute to cancer progression. In this way, the exosomal miR-214 from osteoclasts and lung adenocarcinoma cells mediates the positive interaction between bone resorption and bone metastasis. The levels of exosomal miR-214 in the peripheral circulation may help predict the risk of bone metastasis. The exosomal miR-214 may be a potential therapeutic target for both prevention and treatment of bone metastasis in patients with lung adenocarcinoma.

scholarly journals Lung adenocarcinoma cell-derived exosomal miR-328 promote osteoclastogenesis by targeting Nrp2

2021 ◽  
Author(s):  
Cheng Cheng Zhang ◽  
Jingru Qin ◽  
Lu Yang ◽  
Zhiyao Zhu ◽  
Xinle Qian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Bone Resorption ◽  
Lung Adenocarcinoma ◽  
Adenocarcinoma Cell ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Bone metastasis of lung cancer and detailed mechanisms are still elusive, and the roles of exosomes derived from lung adenocarcinoma cells in this process have attracted much attention. In this study, we found that lung adenocarcinoma cell-derived exosomes (LCC-Exos) promoted osteogenesis and bone resorption in vitro. Furthermore, LCC-Exos target bone in vivo and promoted bone resorption in vivo. Mechanistically, LCC-Exosomal miR-328 promoted bone resorption by targeting Nrp2 and LCC-ExosmiR-328 Inhibitors inhibited bone resorption in vivo. Thus, LCC-Exosomal miR-328 promote osteoclastogenesis by targeting Nrp2 and LCC-ExosmiR-328 Inhibitors may serve as a potential nanomedicine for the treatment of bone metastasis.

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

2018 ◽  
Vol 49 (3) ◽  
pp. 911-919 ◽  
Author(s):  
Xin Yan ◽  
Hua Shen ◽  
Hongjian Jiang ◽  
Dan Hu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathways ◽  
Cytotoxic Effect ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Mesenchymal Transition ◽  
Tgf Β1

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.

scholarly journals Siomycin A Induces Apoptosis in Human Lung Adenocarcinoma A549 Cells by Suppressing the Expression of FoxM1

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Xuedan Guo ◽  
Aiping Liu ◽  
Hongxia Hua ◽  
Huifen Lu ◽  
Dandan Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Human Lung ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Human Lung Adenocarcinoma ◽  
Forkhead Box M1 ◽  
Lung Adenocarcinoma A549 ◽  
Induced Apoptosis ◽  
Siomycin A

Forkhead box M1 (FoxM1), a transcription factor of the Forkhead family, is demonstrated to be critical for proliferation, apoptosis, migration and invasion of lung cancer. In this study, we extensively investigated the anticancer effect of siomycin A, which was identified as an inhibitor of FoxM1 transcriptional activity, on human lung adenocarcinoma A549 cells. Our study indicated that treatment with siomycin A resulted in the suppression of FoxM1 expression, which consequently contributed to its effect of cell growth inhibition and cell apoptosis induction in A549 cells. Then the molecular mechanism of siomycin A's apoptotic action on A549 cells was further investigated. The results revealed that siomycin A induced apoptosis by influencing the downstream events of FoxM1, including inhibiting the expression of Bcl-2 and Mcl-1, as well as leading to caspase-3 cleavage. Taken together, our findings may be useful for understanding the mechanism of action of siomycin A on lung cancer cells and provide new insights into the possible application of such a compound in lung cancer therapy in the future.

scholarly journals MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Lei Han ◽  
Zeyong Huang ◽  
Yan Liu ◽  
Lijuan Ye ◽  
Dongqi Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients

AbstractBone metastasis is one of the most serious complications in lung cancer patients. MicroRNAs (miRNAs) play important roles in tumour development, progression and metastasis. A previous study showed that miR-106a is highly expressed in the tissues of lung adenocarcinoma with bone metastasis, but its mechanism remains unclear. In this study, we showed that miR-106a expression is dramatically increased in lung cancer patients with bone metastasis (BM) by immunohistochemical analysis. MiR-106a promoted A549 and SPC-A1 cell proliferation, migration and invasion in vitro. The results of bioluminescence imaging (BLI), micro-CT and X-ray demonstrated that miR-106a promoted bone metastasis of lung adenocarcinoma in vivo. Mechanistic investigations revealed that miR-106a upregulation promoted metastasis by targeting tumour protein 53-induced nuclear protein 1 (TP53INP1)-mediated metastatic progression, including cell migration, autophagy-dependent death and epithelial–mesenchymal transition (EMT). Notably, autophagy partially attenuated the effects of miR-106a on promoting bone metastasis in lung adenocarcinoma. These findings demonstrated that restoring the expression of TP53INP1 by silencing miR-106a may be a novel therapeutic strategy for bone metastatic in lung adenocarcinoma.

scholarly journals MiR-186 Suppressed Growth, Migration, and Invasion of Lung Adenocarcinoma Cells via Targeting Dicer1

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Juan Wang ◽  
Yi Zhang ◽  
Fanghong Ge
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
A549 Cells ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Ki 67 ◽  
Real Time Quantitative Pcr ◽  
Fatal Form

Objective. Globally, the fatal form of lung cancer is non-small-cell lung cancer (NSCLC), and its most common subtype is lung adenocarcinoma (LUAD). In cancer development and progression, miRNAs play key roles primarily in interacting with cancer-related genes. The main focus of this research was to examine the biological roles of miR-186 in LUAD. Methods. We examined tissues of LUAD and lung cancer cell lines. The expressions of miR-186, Dicer1, Ki-67, and PCNA were determined by immunohistochemistry (IHC), real-time quantitative PCR (RT-PCR), and western blot assays. The CCK-8 and transwell assays were used to determine cell proliferation, migration, and invasion. To determine the association between miR-186 and Dicer1, a luciferase assay was used. Results. MiR-186 expression was found to be lower in LUAD tissues, and this was correlated to TNM stage and lymph node metastasis in LUAD patients. miR-186 upregulation significantly reduced the proliferation rate and the level of Ki67 and PCNA of LUAD cell lines HCC827 and A549. Transwell assay exhibited that miR-186 upregulation considerably reduced HCC827 and A549 cells' migration and invasion abilities. Furthermore, we also confirmed that Dicer1 was a direct target of miR-186. Importantly, Dicer1 overexpression abolished the suppression of miR-186 mimics on cell proliferation, migration, and invasion of HCC827 and A549 cells. Conclusion. These results indicated that the miR-186/Dicer1 pathway is critical for regulating LUAD cell proliferation, migration, and invasion.

scholarly journals Sevoflurane induces lung cancer cell apoptosis via inhibition of the expression of miRNA155 gene

2021 ◽  
Vol 20 (1) ◽  
pp. 69-74
Author(s):  
Huaizhao Wang ◽  
Bin Wang ◽  
Jingyan Jing ◽  
Na Li
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Lung Cancer Cells ◽  
Control Group ◽  
Sevoflurane Group ◽  
Lung Adenocarcinoma A549

Purpose: To determine the apoptotic effect of sevoflurane on lung cancer cells, and the underlying mechanism of action.Methods: Lung adenocarcinoma A549 cells were cultured for 24 h and divided into control group, 1% sevoflurane group and 3% sevoflurane group. The two levels of sevoflurane were provided through a gas monitor connected to each of the sevoflurane groups. The control group was not treated. Flow cytometry was used to analyze A549 cell apoptosis, while qRT-PCR was used for assay of the levels of miRNA155 in A549 cells. The protein expression of Bcl-2 was determined with immunoblotting. The percentage of apoptosis and levels of miRNA155 and Bcl-2 in the two cell lines were compared.Results: Significant differences in miRNA146a level were seen between the 3 % sevoflurane and control groups at 3 h. There was higher apoptosis in the 3 % sevoflurane group, relative to control, but miRNA155 levels in the 3 % sevoflurane group were generally less than that of the control (p < 0.05). There was lower Bcl-2 content in the 3 % sevoflurane group than in control group (p < 0.05).Conclusion: Sevoflurane exerts strong apoptotic and anti-proliferative effects on lung adenocarcinoma A549 cells via a mechanism which may be related to the downregulation of miRNA155, thereby inhibiting the expression of anti-apoptotic protein Bcl-2. This provides a new direction for research on anti-lung adenocarcinoma drugs. Keywords: Sevoflurane, Lung cancer cells, Apoptosis, Inhibition, miRNA155, Expression, Induction

scholarly journals Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 638
Author(s):  
Kittipong Sanookpan ◽  
Nongyao Nonpanya ◽  
Boonchoo Sritularak ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

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