scholarly journals TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression

2021 ◽  
Vol 9 ◽  
Author(s):  
Chunfeng Xie ◽  
Jianyun Zhu ◽  
Xue Yang ◽  
Cong Huang ◽  
Liping Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tobacco Smoke ◽  
Epithelial Mesenchymal Transition ◽  
Suppressor Gene ◽  
Inhibitory Effect ◽  
Vimentin Expression ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients ◽  
Anti Cancer

As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.

scholarly journals Epithelial-mesenchymal transition-associated secretory phenotype predicts survival in lung cancer patients

2014 ◽  
Vol 35 (6) ◽  
pp. 1292-1300 ◽  
Author(s):  
A. K. Reka ◽  
G. Chen ◽  
R. C. Jones ◽  
R. Amunugama ◽  
S. Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients ◽  
Secretory Phenotype

scholarly journals Triptolide suppresses the growth and metastasis of non-small cell lung cancer by inhibiting β-catenin-mediated epithelial–mesenchymal transition

2021 ◽  
Author(s):  
Qiu-di Deng ◽  
Xue-ping Lei ◽  
Yi-hang Zhong ◽  
Min-shan Chen ◽  
Yuan-yu Ke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Small Cell ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Small Cell Lung ◽  
Mesenchymal Transition

AbstractNon-small cell lung cancer (NSCLC) is characterized by a high incidence of metastasis and poor survival. As epithelial–mesenchymal transition (EMT) is well recognized as a major factor initiating tumor metastasis, developing EMT inhibitor could be a feasible treatment for metastatic NSCLC. Recent studies show that triptolide isolated from Tripterygium wilfordii Hook F attenuated the migration and invasion of breast cancer, colon carcinoma, and ovarian cancer cells, and EMT played important roles in this process. In the present study we investigated the effect of triptolide on the migration and invasion of NSCLC cell lines. We showed that triptolide (0.5, 1.0, 2.0 nM) concentration-dependently inhibited the migration and invasion of NCI-H1299 cells. Triptolide treatment concentration-dependently suppressed EMT in NCI-H1299 cells, evidenced by significantly elevated E-cadherin expression and reduced expression of ZEB1, vimentin, and slug. Furthermore, triptolide treatment suppressed β-catenin expression in NCI-H1299 and NCI-H460 cells, overexpression of β-catenin antagonized triptolide-caused inhibition on EMT, whereas knockout of β-catenin enhanced the inhibitory effect of triptolide on EMT. Administration of triptolide (0.75, 1.5 mg/kg per day, ip, every 2 days) for 18 days in NCI-H1299 xenograft mice dose-dependently suppressed the tumor growth, restrained EMT, and decreased lung metastasis, as evidence by significantly decreased expression of mesenchymal markers, increased expression of epithelial markers as well as reduced number of pulmonary lung metastatic foci. These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing β-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.

Recent Advances in Elucidating Paclitaxel Resistance Mechanisms in Non-small Cell Lung Cancer and Strategies to Overcome Drug Resistance

2020 ◽  
Vol 27 (39) ◽  
pp. 6573-6595
Author(s):  
Hongmei Cui ◽  
Kinsie Arnst ◽  
Duane D. Miller ◽  
Wei Li
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Resistance Mechanisms ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients ◽  
Nsclc Patients

Paclitaxel (PTX) is a first-line drug for late-stage non-small cell lung cancer (NSCLC) patients who do not benefit from targeted therapy or immunotherapy. However, patients invariably develop resistance to PTX upon prolonged treatments. Although diverse mechanisms leading to PTX resistance have been well-documented in the literature, strategies to overcome PTX resistance in NSCLC based on these mechanisms are still challenging. In this article, we reviewed recent advancements elucidating major mechanisms of PTX resistance in NSCLC, including the overexpression of ABC transporters, alternations to tubulin structures, and the involvement of cytokines, miRNAs, kinase signaling pathways, and epithelial-mesenchymal transition. Potential markers of PTX resistance or PTX response that could help to direct treatment decisions and restore cellular sensitivity to PTX were also discussed. Finally, we summarized the corresponding strategies to overcome PTX resistance in NSCLC cells, which might provide new insights into clinical trials and benefit lung cancer patients in the future.

scholarly journals Clinico-Pathological Importance of miR-146a in Lung Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 274
Author(s):  
Javaid Ahmad Wani ◽  
Sabhiya Majid ◽  
Andleeb Khan ◽  
Azher Arafah ◽  
Ajaz Ahmad ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Research Field ◽  
Stem Loop ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Actual Mechanism ◽  
Micro Rnas

Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health in the 21st century. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 20–25 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz. TNF-α, NF-κB and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.

scholarly journals TFIIB-Related Factor 2 Is Associated with Poor Prognosis of Nonsmall Cell Lung Cancer Patients through Promoting Tumor Epithelial-Mesenchymal Transition

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Yu Tian ◽  
Ming Lu ◽  
Weiming Yue ◽  
Lin Li ◽  
Shuhai Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Nonsmall Cell Lung Cancer ◽  
Related Factor ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients ◽  
The Poor ◽  
Tumor Tissues ◽  
Nsclc Patients

In this study, we found that increased BRF2 protein expression was prevalent in NSCLC. Overexpression of BRF2 correlated with abnormal expression of E-cadherin, N-cadherin, and snail. Additionally, expression of BRF2 was found to be an independent prognostic factor in NSCLC patients. Furthermore, we showed that targeted knockdown of BRF2 expression could inhibit the migratory and invasive abilities of NSCLC cells and induced loss of the epithelial-mesenchymal transition of NSCLC cells. These results suggested that BRF2 overexpression in tumor tissues is significantly associated with the poor prognosis of NSCLC patients through promoting epithelial-mesenchymal transition (EMT) program.

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 Non-invasive detection of epithelial mesenchymal transition phenotype and metastatic dissemination of lung cancer by liquid biopsy

2021 ◽  
Author(s):  
Viviana De Rosa ◽  
Rosa Fonti ◽  
Silvana Del Vecchio ◽  
Francesca Iommelli
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Liquid Biopsy ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Cell ◽  
Mesenchymal Transition ◽  
Metastatic Dissemination ◽  
Lung Cancer Patients ◽  
Non Invasive

The occurrence of phenotype switch from an epithelial to a mesenchymal cell state during the activation of the epithelial mesenchymal transition (EMT) program in cancer cells has been closely associated with the generation of invasive tumor cells that contribute to metastatic dissemination and treatment failure. Liquid biopsy represents an emergent non-invasive tool that may improve our understanding of the molecular events leading to cancer progression and initiating the metastatic cascade through the dynamic analysis of tumor-derived components isolated from body fluids. The present review will primarily focus on the applications of liquid biopsy in lung cancer patients for identifying EMT signature, elucidating molecular mechanisms underlying the acquisition of an invasive phenotype and detecting new targets for therapy.

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