Practicability of clinical application of bladder cancer molecular classification and additional value of epithelial-to-mesenchymal transition: prognostic value of vimentin expression

Gallbladder cancer (GBC), a rare but lethal disease, is often diagnosed at advanced stages. So far, molecular characterization of GBC is insufficient, and a comprehensive molecular portrait is warranted to uncover new targets and classify GBC. We performed a transcriptome analysis of both coding and non-coding RNAs from 36 GBC fresh-frozen samples. The results were integrated with those of comprehensive mutation profiling based on whole-genome or exome sequencing. The clustering analysis of RNA-seq data facilitated the classification of GBCs into two subclasses, characterized by high or low expression levels of TME (tumor microenvironment) genes. A correlation was observed between gene expression and pathological immunostaining. TME-rich tumors showed significantly poor prognosis and higher recurrence rate than TME-poor tumors. TME-rich tumors showed overexpression of genes involved in epithelial-to-mesenchymal transition (EMT) and inflammation or immune suppression, which was validated by immunostaining. One non-coding RNA, miR125B1, exhibited elevated expression in stroma-rich tumors, and miR125B1 knockout in GBC cell lines decreased its invasion ability and altered the EMT pathway. Mutation profiles revealed TP53 (47%) as the most commonly mutated gene, followed by ELF3 (13%) and ARID1A (11%). Mutations of ARID1A, ERBB3, and the genes related to the TGF-β signaling pathway were enriched in TME-rich tumors. This comprehensive analysis demonstrated that TME, EMT, and TGF-β pathway alterations are the main drivers of GBC and provides a new classification of GBCs that may be useful for therapeutic decision-making.

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HMMR is a downstream target of FOXM1 in enhancing proliferation and partial epithelial-to-mesenchymal transition of bladder cancer cells

Experimental Cell Research ◽

10.1016/j.yexcr.2021.112860 ◽

2021 ◽

pp. 112860

Author(s):

Dong Yang ◽

Yan Ma ◽

Pengcheng Zhao ◽

Jing Ma ◽

Chaohong He

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Mesenchymal Transition ◽

Downstream Target ◽

Bladder Cancer Cells

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Circular RNA circMTO1 suppresses bladder cancer metastasis by sponging miR-221 and inhibiting epithelial-to-mesenchymal transition

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.12.046 ◽

2019 ◽

Vol 508 (4) ◽

pp. 991-996 ◽

Cited By ~ 33

Author(s):

Yixiao Li ◽

Bo Wan ◽

Lei Liu ◽

Lei Zhou ◽

Qing Zeng

Keyword(s):

Bladder Cancer ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

Circular Rna ◽

Mesenchymal Transition

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Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

Molecules ◽

10.3390/molecules26195858 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5858

Author(s):

Baris Kucukkaraduman ◽

Ekin Gokce Cicek ◽

Muhammad Waqas Akbar ◽

Secil Demirkol Canli ◽

Burcak Vural ◽

...

Keyword(s):

Natural Products ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Epithelial To Mesenchymal Transition ◽

Epigallocatechin Gallate ◽

Cancer Cell Lines ◽

Vimentin Expression ◽

Mesenchymal Transition ◽

Urolithin A

Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.

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Circular RNA CircPPP1CB Suppresses Tumorigenesis by Interacting With the MiR-1307-3p/SMG1 Axis in Human Bladder Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.704683 ◽

2021 ◽

Vol 9 ◽

Author(s):

Feifan Wang ◽

Yan Zhang ◽

Xuejian Zhou ◽

Xianwu Chen ◽

Jiayong Xiang ◽

...

Keyword(s):

Bladder Cancer ◽

Epithelial To Mesenchymal Transition ◽

Human Cancer ◽

Circular Rna ◽

Human Bladder Cancer ◽

Human Bladder ◽

Mesenchymal Transition ◽

Circular Structure

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA (ncRNA), which is characterized with a closed circular structure. A growing body of evidence has verified the vital roles of circRNAs in human cancer. In this research, we selected circPPP1CB as a study object by circRNA sequencing and quantitative real-time PCR (qRT-PCR) validation in human bladder cancer (BC). CircPPP1CB is downregulated in BC and is negatively correlated with clinical stages and histological grades. Functionally, circPPP1CB modulated cell growth, metastasis, and epithelial-to-mesenchymal transition (EMT) process in vitro and in vivo. Mechanically, we performed various experiments to verify the circPPP1CB/miR-1307-3p/SMG1 regulatory axis. Taken together, our results demonstrated that circPPP1CB participates in tumor growth, metastasis, and EMT process by interacting with the miR-1307-3p/SMG1 axis, and that circPPP1CB might be a novel therapeutic target and diagnostic biomarker in human BC.

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50 Silencing Notch-1 and Notch-3 promotes epithelial-to-mesenchymal transition (EMT) and self-renewal potential in human bladder cancer

European Urology Supplements ◽

10.1016/s1569-9056(13)60543-6 ◽

2013 ◽

Vol 12 (1) ◽

pp. e50

Author(s):

W. Jaeger ◽

T. Hayashi ◽

S. Awrey ◽

K.M. Gust ◽

T. Cordonnier ◽

...

Keyword(s):

Bladder Cancer ◽

Epithelial To Mesenchymal Transition ◽

Human Bladder Cancer ◽

Notch 1 ◽

Human Bladder ◽

Self Renewal ◽

Mesenchymal Transition ◽

Notch 3

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A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability

Cancers ◽

10.3390/cancers12071863 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1863

Author(s):

Mauricio P. Pinto ◽

Miguel Córdova-Delgado ◽

Ignacio N. Retamal ◽

Matías Muñoz-Medel ◽

M. Loreto Bravo ◽

...

Keyword(s):

Gastric Cancer ◽

Latin American ◽

Epithelial To Mesenchymal Transition ◽

Low Cost ◽

Molecular Classification ◽

The Cancer Genome Atlas ◽

Mesenchymal Transition ◽

Barr Virus ◽

Clinical Applicability ◽

Stratification System

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein–Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53−). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic

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Vimentin as a target for the treatment of COVID-19

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2020-000623 ◽

2020 ◽

Vol 7 (1) ◽

pp. e000623

Author(s):

Zhenlin Li ◽

Denise Paulin ◽

Patrick Lacolley ◽

Dario Coletti ◽

Onnik Agbulut

Keyword(s):

Viral Infection ◽

Lung Inflammation ◽

Epithelial To Mesenchymal Transition ◽

Attachment Site ◽

Vimentin Expression ◽

Mesenchymal Transition ◽

Cellular Target ◽

Innovative Idea ◽

Life Threatening ◽

Approved Drugs

We and others propose vimentin as a possible cellular target for the treatment of COVID-19. This innovative idea is so recent that it requires further attention and debate. The significant role played by vimentin in virus-induced infection however is well established: (1) vimentin has been reported as a co-receptor and/or attachment site for SARS-CoV; (2) vimentin is involved in viral replication in cells; (3) vimentin plays a fundamental role in both the viral infection and the consequent explosive immune-inflammatory response and (4) a lower vimentin expression is associated with the inhibition of epithelial to mesenchymal transition and fibrosis. Moreover, the absence of vimentin in mice makes them resistant to lung injury. Since vimentin has a twofold role in the disease, not only being involved in the viral infection but also in the associated life-threatening lung inflammation, the use of vimentin-targeted drugs may offer a synergistic advantage as compared with other treatments not targeting vimentin. Consequently, we speculate here that drugs which decrease the expression of vimentin can be used for the treatment of patients with COVID-19 and advise that several Food and Drug Administration-approved drugs be immediately tested in clinical trials against SARS-CoV-2, thus broadening therapeutic options for this type of viral infection.

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