MicroRNA-32-5p inhibits epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting SMAD family 3

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

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Prognostic impact of microscopic vessel invasion and visceral pleural invasion and their correlations with epithelial–mesenchymal transition, cancer stemness, and treatment failure in lung adenocarcinoma

Lung Cancer ◽

10.1016/j.lungcan.2018.12.001 ◽

2019 ◽

Vol 128 ◽

pp. 13-19 ◽

Cited By ~ 2

Author(s):

Shinya Neri ◽

Toshi Menju ◽

Terumasa Sowa ◽

Yojiro Yutaka ◽

Daisuke Nakajima ◽

...

Keyword(s):

Treatment Failure ◽

Lung Adenocarcinoma ◽

Epithelial Mesenchymal Transition ◽

Prognostic Impact ◽

Cancer Stemness ◽

Mesenchymal Transition ◽

Pleural Invasion ◽

Vessel Invasion ◽

Visceral Pleural Invasion

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lncCRLA enhanced chemoresistance in lung adenocarcinoma that underwent epithelial-mesenchymal transition

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504021x16203818567367 ◽

2021 ◽

Author(s):

Weili Min ◽

Liangzhang Sun ◽

Burong Li ◽

Xiao Gao ◽

Shuqun Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Epithelial Mesenchymal Transition ◽

Chemotherapy Resistance ◽

Metastatic Potential ◽

Caspase 8 ◽

Mesenchymal Transition ◽

Adenocarcinoma Cells ◽

Signaling Axis ◽

Lung Adenocarcinoma Cells ◽

Paclitaxel Liposome

EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated Caspase-8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel inpatients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of Caspase-8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency of Caspase-8, during which FADD interacted with RIPK1 to activateRIPK1/RIPK3/MLKL signaling axis. Accompanied with c-Src-mediated Caspase-8 phosphorylation to trigger EMT, a novel lncRNA named lncCRLA was markedly upregulated and inhibited RIPK1-induced necroptosis by impairing RIPK1-RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinib mitigated c-Src-mediated phosphorylation of Caspase-8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung adenocarcinoma cells to paclitaxel+dasatinib. c-Src-Caspase-8 interaction initiates EMT and chemoresistance viaCaspase-8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome+siFLIP regimen was lethal.

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Radiological features of resected lung adenocarcinoma with epithelial–mesenchymal transition

The Annals of Thoracic Surgery ◽

10.1016/j.athoracsur.2020.10.034 ◽

2020 ◽

Author(s):

Taichi Matsubara ◽

Tetsuzo Tagawa ◽

Gouji Toyokawa ◽

Takeshi Kamitani ◽

Kazuki Takada ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Radiological Features

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Linc00426 accelerates lung adenocarcinoma progression by regulating miR-455-5p as a molecular sponge

Cell Death and Disease ◽

10.1038/s41419-020-03259-2 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Hongli Li ◽

Qingjie Mu ◽

Guoxin Zhang ◽

Zhixin Shen ◽

Yuanyuan Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Ectopic Expression ◽

Tumor Development ◽

Biological Significance ◽

Mesenchymal Transition

AbstractIncreasing lines of evidence indicate the role of long non-coding RNAs (LncRNAs) in gene regulation and tumor development. Hence, it is important to elucidate the mechanisms of LncRNAs underlying the proliferation, metastasis, and invasion of lung adenocarcinoma (LUAD). We employed microarrays to screen LncRNAs in LUAD tissues with and without lymph node metastasis and revealed their effects on LUAD. Among them, Linc00426 was selected for further exploration in its expression, the biological significance, and the underlying molecular mechanisms. Linc00426 exhibits ectopic expression in LUAD tissues and cells. The ectopic expression has been clinically linked to tumor size, lymphatic metastasis, and tumor differentiation of patients with LUAD. The deregulation of Linc00426 contributes to a notable impairment in proliferation, invasion, metastasis, and epithelial–mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the deregulation of Linc00426 could reduce cytoskeleton rearrangement and matrix metalloproteinase expression. Meanwhile, decreasing the level of Linc00426 or increasing miR-455-5p could down-regulate the level of UBE2V1. Thus, Linc00426 may act as a competing endogenous RNA (ceRNA) to abate miR-455-5p-dependent UBE2V1 reduction. We conclude that Linc00426 accelerates LUAD progression by acting as a molecular sponge to regulate miR-455-5p, and may be a potential novel tumor marker for LUAD.

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Targeting β-tubulin/CCT-β complex induces apoptosis and suppresses migration and invasion of highly metastatic lung adenocarcinoma

Carcinogenesis ◽

10.1093/carcin/bgz137 ◽

2019 ◽

Vol 41 (5) ◽

pp. 699-710 ◽

Cited By ~ 3

Author(s):

Yan-Jin Liu ◽

Yu-Ju Chang ◽

Yu-Ting Kuo ◽

Po-Huang Liang

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cancer Cells ◽

Prognostic Marker ◽

Epithelial Mesenchymal Transition ◽

Lung Cancer Cell Line ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Metastatic Lung ◽

Β Tubulin

Abstract Metastasis, the movement of cancer cells from one site to another, is responsible for the highest number of cancer deaths, especially in lung cancer patients. In this study, we first identified a prognostic marker of lung adenocarcinoma, TCP-1 β subunit (chaperonin-containing TCP-1β; CCT-β). We showed a compound that disrupted the interaction of CCT-β with β-tubulin killed a highly metastatic non-small cell lung cancer cell line CL1-5 through inducing Endoplasmic reticulum stress and caspases activation. Moreover, at the dosage of EC20, the compound inhibited migration and invasion of the lung cancer cells by suppressing matrix metalloproteinase (MMP)-2/9 and epithelial–mesenchymal transition (EMT)-related proteins through downregulating mitogen-activated protein kinases (MAPKs), Akt/β-catenin and integrin–focal adhesion kinase signaling pathways. Unlike the anticancer drugs, such as Taxol, that target the adenosine triphosphate site of β-tubulin, this study reveals a therapeutic target, β-tubulin/CCT-β complex, for metastatic human lung adenocarcinoma. The study demonstrated CCT-β as a prognostic marker. Targeting β-tubulin/CCT-β complex caused apoptosis and inhibited invasion/migration of CCT-β overexpressed, highly metastatic lung adenocarcinoma.

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Co-Expression of Coxsackievirus/Adenovirus Receptors and Desmoglein 2 in Lung Adenocarcinoma: A Comprehensive Analysis of Bioinformatics and Tissue Microarrays

Journal of Clinical Medicine ◽

10.3390/jcm9113693 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3693

Author(s):

Ching-Fu Weng ◽

Chi-Jung Huang ◽

Mei-Hsuan Wu ◽

Henry Hsin-Chung Lee ◽

Thai-Yen Ling

Keyword(s):

Overall Survival ◽

Survival Analysis ◽

Lung Adenocarcinoma ◽

Cox Regression ◽

Epithelial Mesenchymal Transition ◽

Early Stage ◽

The Cancer Genome Atlas ◽

Cancer Tissue ◽

Mesenchymal Transition ◽

Kaplan Meier

Introduction: Coxsackievirus/adenovirus receptors (CARs) and desmoglein-2 (DSG2) are similar molecules to adenovirus-based vectors in the cell membrane. They have been found to be associated with lung epithelial cell tumorigenesis and can be useful markers in predicting survival outcome in lung adenocarcinoma (LUAD). Methods: A gene ontology enrichment analysis disclosed that DSG2 was highly correlated with CAR. Survival analysis was then performed on 262 samples from the Cancer Genome Atlas, forming “Stage 1A” or “Stage 1B”. We therefore analyzed a tissue microarray (TMA) comprised of 108 lung samples and an immunohistochemical assay. Computer counting software was used to calculate the H-score of the immune intensity. Cox regression and Kaplan–Meier analyses were used to determine the prognostic value. Results: CAR and DSG2 genes are highly co-expressed in early stage LUAD and associated with significantly poorer survival (p = 0.0046). TMA also showed that CAR/DSG2 expressions were altered in lung cancer tissue. CAR in the TMA was correlated with proliferation, apoptosis, and epithelial–mesenchymal transition (EMT), while DSG2 was associated with proliferation only. The Kaplan–Meier survival analysis revealed that CAR, DSG2, or a co-expression of CAR/DSG2 was associated with poorer overall survival. Conclusions: The co-expression of CAR/DSG2 predicted a worse overall survival in LUAD. CAR combined with DSG2 expression can predict prognosis.

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RUFY3 Predicts Poor Prognosis and Promotes Metastasis through Epithelial-mesenchymal Transition in Lung Adenocarcinoma

Journal of Cancer ◽

10.7150/jca.35072 ◽

2019 ◽

Vol 10 (25) ◽

pp. 6278-6285 ◽

Cited By ~ 1

Author(s):

Wanfu Men ◽

Wenya Li ◽

Yu Li ◽

Jungang Zhao ◽

Xiaohan Qu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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Inhibitor of DNA-Binding Protein 4 Suppresses Cancer Metastasis through the Regulation of Epithelial Mesenchymal Transition in Lung Adenocarcinoma

Cancers ◽

10.3390/cancers11122021 ◽

2019 ◽

Vol 11 (12) ◽

pp. 2021 ◽

Cited By ~ 1

Author(s):

Chi-Chung Wang ◽

Yuan-Ling Hsu ◽

Chi-Jen Chang ◽

Chia-Jen Wang ◽

Tzu-Hung Hsiao ◽

...

Keyword(s):

Lung Cancer ◽

Dna Binding ◽

Lung Adenocarcinoma ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Inhibitor Of Dna Binding ◽

E Cadherin

Metastasis is a predominant cause of cancer death and the major challenge in treating lung adenocarcinoma (LADC). Therefore, exploring new metastasis-related genes and their action mechanisms may provide new insights for developing a new combative approach to treat lung cancer. Previously, our research team discovered that the expression of the inhibitor of DNA binding 4 (Id4) was inversely related to cell invasiveness in LADC cells by cDNA microarray screening. However, the functional role of Id4 and its mechanism of action in lung cancer metastasis remain unclear. In this study, we report that the expression of Id4 could attenuate cell migration and invasion in vitro and cancer metastasis in vivo. Detailed analyses indicated that Id4 could promote E-cadherin expression through the binding of Slug, cause the occurrence of mesenchymal-epithelial transition (MET), and inhibit cancer metastasis. Moreover, the examination of the gene expression database (GSE31210) also revealed that high-level expression of Id4/E-cadherin and low-level expression of Slug were associated with a better clinical outcome in LADC patients. In summary, Id4 may act as a metastatic suppressor, which could not only be used as an independent predictor but also serve as a potential therapeutic for LADC treatment.

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