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

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.

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

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.645402 ◽

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.

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LncRNA MIAT as a Stemness-Associated Transcript Regulates the Proliferation, Migration and Metastasis of Glioma

10.21203/rs.3.rs-619425/v1 ◽

2021 ◽

Author(s):

Farzane Amirmahani ◽

Malek Hossein Asadi ◽

Sadeq Vallian

Keyword(s):

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Migration Ability ◽

Altered Expression ◽

Mesenchymal Transition ◽

Cycle Arrest ◽

Non Coding Rna ◽

Tumor Tissues ◽

Micro Rnas ◽

Induced Apoptosis

Abstract Purpose: Glioma is the most prevalent category of brain tumors with cancer stem cells. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA), with altered expression in different diseases and cancers. The purpose of this study was to evaluate the functional role of lncRNA MIAT in glioma.Methods: In this study, lncRNA MIAT expression was evaluated in the TCGA database in common cancers and glioma specimens. The expression of lncRNA MIAT was knocked down by the RNA interference method, and its effects on the characteristics of two glioma cancer cell lines, A172 and U-87MG, were investigated. Results: The findings of the bioinformatics analysis showed an increase in the expression level of lncRNA MIAT in 12 common cancers. The expression of lncRNA MIAT was much greater in glioma tumor tissues compared to other ones. Knocking-down of lncRNA MIAT led to the reduction of proliferation of glioma cancer cells followed by cell cycle arrest at G1 phase. Furthermore, the inhibition of expression of lncRNA MIAT significantly induced apoptosis, senescence and autophagy, but limited the migration ability and Epithelial-Mesenchymal-Transition (EMT) of cancer cells. Moreover, knocking-down of lncRNA MIAT reduced the expression of stemness factors including Oct4, Sox2, and Nanog. This resulted in the upregulation of their downstream miRNAs (micro RNAs), let-7a-5p and miR-29b-3p. Conclusion: Altogether, our findings showed that lncRNA MIAT could control proliferation, migration and metastasis of glioma cells by regulating the Nanog/ Sox2 / MAP1LC3B2/ let-7a-5p / miR-29b-3p axis. These observations proposed that lncRNA MIAT could be considered as a new oncogene in glioma.

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Transcriptomic and metabolomic profiling reveal the p53-dependent benzeneacetic acid attenuation of silica‐induced epithelial–mesenchymal transition in human bronchial epithelial cells

Cell & Bioscience ◽

10.1186/s13578-021-00545-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhao Ju ◽

Jianlin Shao ◽

Meiling Zhou ◽

Jing Jin ◽

Huiji Pan ◽

...

Keyword(s):

Epithelial Cells ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Dependent Manner ◽

Altered Expression ◽

Bronchial Epithelial ◽

Mesenchymal Transition ◽

Silica Exposure ◽

Biomarker Research ◽

Benzeneacetic Acid

Abstract Background Silica exposure underlies the development of silicosis, one of the most serious occupational hazards worldwide. We aimed to explore the interaction of the silica-induced epithelial–mesenchymal transition (EMT)-related transcripts with the cellular metabolism regulated by p53. Methods We knocked out p53 using CRISPR/Cas9 in the human bronchial epithelial (HBE) cell line. The transcriptomic and metabolomic analyses and integrative omics were conducted using microarrays, GC–MS, and MetaboAnalyst, respectively. Results Fifty-two mRNAs showed significantly altered expression in the HBE p53-KO cells post-silica exposure. A total of 42 metabolites were putatively involved in p53-dependent silica-mediated HBE cell dysfunction. Through integrated data analysis, we obtained five significant p53-dependent metabolic pathways including phenylalanine, glyoxylate, dicarboxylate, and linoleic acid metabolism, and the citrate cycle. Through metabolite screening, we further identified that benzeneacetic acid, a key regulation metabolite in the phenylalanine metabolic pathway, attenuated the silica-induced EMT in HBE cells in a p53-dependent manner. Interestingly, despite the extensive p53-related published literature, the clinical translation of these studies remains unsubstantial. Conclusions Our study offers new insights into the molecular mechanisms by which epithelial cells respond to silica exposure and provide fresh perspective and direction for future clinical biomarker research and potential clinically sustainable and translatable role of p53.

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Transcriptomic and Metabolomic Profiling Reveal the p53-Dependent Benzeneacetic Acid Attenuation of Silica-Induced Epithelial–Mesenchymal Transition in Human Bronchial Epithelial Cells

10.21203/rs.3.rs-54831/v1 ◽

2020 ◽

Author(s):

Meiling Zhou ◽

Zhao Ju ◽

Jing Jin ◽

Huiji Pan ◽

Ping Ding ◽

...

Keyword(s):

Epithelial Cells ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Dependent Manner ◽

Altered Expression ◽

Bronchial Epithelial ◽

Mesenchymal Transition ◽

Silica Exposure ◽

Biomarker Research ◽

Benzeneacetic Acid

Abstract Background: Silica exposure underlies the development of silicosis, one of the most serious occupational hazards worldwide. We aimed to explore the interaction of the silica-induced epithelial–mesenchymal transition (EMT)-related transcripts with the cellular metabolism regulated by p53.Methods: We knocked out p53 using CRISPR/Cas9 in the human bronchial epithelial (HBE) cell line. The transcriptomic and metabolomic analyses and integrative omics were conducted using microarrays, GC-MS, and MetaboAnalyst, respectively. Results: Fifty-two mRNAs showed significantly altered expression in the HBE p53-KO cells post-silica exposure. A total of 42 metabolites were putatively involved in p53-dependent silica-mediated HBE cell dysfunction. Through integrated data analysis, we obtained five significant p53-dependent metabolic pathways including phenylalanine, glyoxylate, dicarboxylate, and linoleic acid metabolism, and the citrate cycle. Through metabolite screening, we further identified that benzeneacetic acid, a key regulation metabolite in the phenylalanine metabolic pathway, attenuated the silica-induced EMT in HBE cells ina p53-dependent manner. Interestingly, despite the extensive p53-related published literature, the clinical translation of these studies remains unsubstantial. Conclusions: Our study offers new insights into the molecular mechanisms by which epithelial cells respond to silica exposure and provide fresh perspective and direction for future clinical biomarker research and potential clinically sustainable and translatable role of p53.

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Genetically Engineered Lung Cancer Cells for Analyzing Epithelial–Mesenchymal Transition

Cells ◽

10.3390/cells8121644 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1644

Author(s):

Michał Kiełbus ◽

Jakub Czapiński ◽

Joanna Kałafut ◽

Justyna Woś ◽

Andrzej Stepulak ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Fluorescent Protein ◽

Epithelial Mesenchymal Transition ◽

Genetically Engineered ◽

Lung Cancer Cells ◽

Gene Marker ◽

Cellular Plasticity ◽

Mesenchymal Transition

Cell plasticity, defined as the ability to undergo phenotypical transformation in a reversible manner, is a physiological process that also exerts important roles in disease progression. Two forms of cellular plasticity are epithelial–mesenchymal transition (EMT) and its inverse process, mesenchymal–epithelial transition (MET). These processes have been correlated to the poor outcome of different types of neoplasias as well as drug resistance development. Since EMT/MET are transitional processes, we generated and validated a reporter cell line. Specifically, a far-red fluorescent protein was knocked-in in-frame with the mesenchymal gene marker VIMENTIN (VIM) in H2170 lung cancer cells. The vimentin reporter cells (VRCs) are a reliable model for studying EMT and MET showing cellular plasticity upon a series of stimulations. These cells are a robust platform to dissect the molecular mechanisms of these processes, and for drug discovery in vitro and in vivo in the future.

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

Exploration of Targeted Anti-tumor Therapy ◽

10.37349/etat.2021.00032 ◽

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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Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2020.609275 ◽

2021 ◽

Vol 10 ◽

Author(s):

Wu-Ping Zheng ◽

Feng-Ying Huang ◽

Shu-Zhen Dai ◽

Jin-Yan Wang ◽

Ying-Ying Lin ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Anticancer Agent ◽

Epithelial Mesenchymal Transition ◽

Lung Cancer Cells ◽

Mesenchymal Transition

Toxicarioside O (TCO), a natural product derived from Antiaris toxicaria, has been identified to be a promising anticancer agent. In this study, we aimed to investigate the effect of TCO on the proliferation and epithelial-mesenchymal transition (EMT) of lung cancer cells and its molecular mechanisms. Here, we indicated that TCO inhibits the proliferation of lung cancer cells both in vitro and in vivo. Our results demonstrated that TCO induces apoptosis in lung cancer cells. Moreover, we found that TCO suppresses EMT program and inhibits cell migration in vitro. Mechanistically, TCO decreases the expression of trophoblast cell surface antigen 2 (Trop2), resulting in inhibition of the PI3K/Akt pathway and EMT program. Overexpression of Trop2 rescues TCO-induced inhibition of cell proliferation and EMT. Our findings demonstrate that TCO markedly inhibits cell proliferation and EMT in lung cancer cells and provides guidance for its drug development.

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Genetical engineered lung cancer cell for analyzing Epithelial-Mesenchymal transition

10.1101/778316 ◽

2019 ◽

Author(s):

Michał Kiełbus ◽

Jakub Czapiński ◽

Joanna Kałafut ◽

Justyna Woś ◽

Andrzej Stepulak ◽

...

Keyword(s):

Lung Cancer ◽

Molecular Mechanisms ◽

Fluorescent Protein ◽

Epithelial Mesenchymal Transition ◽

Gene Marker ◽

Cellular Plasticity ◽

Mesenchymal Transition ◽

Physiological Processes

AbstractCell plasticity, defined as the ability to undergo phenotypical transformation in a reversible manner, is a physiological processes that also exert important roles in disease progression Two forms of cellular plasticity are epithelial-mesenchymal transition (EMT) and its inverse process, mesenchymal-epithelial transition (MET). These processes have been correlated to the poor outcome of different types of neoplasias as well as drug resistance development. Since EMT/MET are transitional processes, we have generated and validated a reporter cell line. Specifically, a far-red fluorescent protein was knocked-in in-frame with the mesenchymal gene marker VIMENTIN (VIM) in H2170 lung cancer cells. The vimentin reporter cells (VRCs) are a reliable model for studying EMT and MET showing cellular plasticity upon a series of stimulations. These cells are a robust platform to dissect the molecular mechanisms of these processes, and for drug discovery in vitro and in the future in vivo.

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FERMT3 Mediates Cigarette Smoke-induced Epithelial-mesenchymal Transition Through Wnt/β-Catenin Signaling

10.21203/rs.3.rs-631671/v1 ◽

2021 ◽

Author(s):

Xiaoshan Su ◽

Junjie Chen ◽

Xiaoping Lin ◽

Xiaoyang Chen ◽

Zhixing Zhu ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cell Migration ◽

Cigarette Smoke ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

A549 Cells ◽

Cigarette Smoke Exposure ◽

Mesenchymal Transition

Abstract Background: Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated. Methods: The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Two GEO datasets were combined to identify FERMT3 involved in COPD. The expression of FERMT3 was identified in COPD from two GEO datasets. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT. Results: Based on the GEO dataset analysis, the expression of FERMT3 was downregulated in COPD-smoker bronchoalveolar lavage fluid than that in Non-smoker. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling. Conclusions: In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/β-Catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

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MiR-597 Targeting 14-3-3σ Enhances Cellular Invasion and EMT in Nasopharyngeal Carcinoma Cells

Current Molecular Pharmacology ◽

10.2174/1874467212666181218113930 ◽

2019 ◽

Vol 12 (2) ◽

pp. 105-114 ◽

Cited By ~ 1

Author(s):

Lisha Xie ◽

Tao Jiang ◽

Ailan Cheng ◽

Ting Zhang ◽

Pin Huang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Lines ◽

Western Blotting ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Suppressor Gene ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Downstream Target ◽

Before And After

Background: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. Methods: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. Results: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. Conclusion: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.

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