A panel of emerging EMT genes identified in malignant mesothelioma

Wu, Licun; Amjad, Shaheer; Yun, Hana; Mani, Sendurai A.; Perrot, Marc de

doi:10.1038/s41598-022-04973-x

Cited by 18 publications

(16 citation statements)

References 48 publications

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“…The in-silico analysis revealed that several targets triggered by miRNA-181a-5p and 193a-5p were involved in mesothelioma development. In particular, we found proteins involved in the regulation of pathways aberrantly activated in mesothelioma, such as MAPK, PI3K-Akt and mTOR signalling pathways [ 4 , 11 , 12 ], as well as the EGFR [ 13 ], Hippo [ 14 , 15 ], epithelial to mesenchymal transition [ 16 ] and NF-kappa B signalling pathways [ 17 , 18 ]. While miRNA-181-5p exerts an inhibitor regulation on those pathways, thereby eliciting a tumor-suppressor effect, miRNA 193-5p had an inverse role.…”

Section: Resultsmentioning

confidence: 99%

Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial

Muti

Sacconi²,

Pulito

et al. 2022

J Exp Clin Cancer Res

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Background Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set. Methods In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model. Results We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants. Conclusions We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma. Trial registration ClinicalTrials.gov, NCT02076672. Registered 03/03/2014.

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Section: Resultsmentioning

confidence: 99%

Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial

Muti

Sacconi²,

Pulito

et al. 2022

J Exp Clin Cancer Res

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“…Furthermore, the function of integrins is not limited to simple mechanical cell adhesion but also influences cell proliferation and other processes by transmitting signals in both directions through the cell membrane [15]. The association between malignant mesothelioma and IT- GAV is primarily unexplored, with the existing reports on ITGAV addressing the genes associated with wound healing and EMT [42,43].…”

Section: Discussionmentioning

confidence: 99%

miR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV

et al. 2023

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Introduction: Malignant mesothelioma is an aggressive cancer associated with asbestos exposure. Currently, the efficacy of therapeutics is limited in malignant mesothelioma, and developing more effective therapies is the need of the hour. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have attracted attention as therapeutic targets. To explore potential therapeutic targets, we focused on miR-142-3p expression, which was found to be significantly downregulated in mesothelioma cell lines in our previous study. Methods: Mesothelioma cell lines and tissues were validated for expression of miR-142-3p or integrin subunit alpha-V (ITGAV). We transfected mesothelioma cell lines with miR-142-3p mimic and ITGAV siRNA and analyzed their biological functions. Results: We found that miR-142-3p was significantly downregulated in mesothelioma tissues. Transfection with miR-142-3p mimic significantly suppressed cell proliferation, migration, and invasion. Bioinformatics analysis of potential targets of miR-142-3p identified ITGAV. Membrane ITGAV expression in mesothelioma cell lines was confirmed using immunocytochemistry. ITGAV was significantly upregulated in mesothelioma tissues. Moreover, transfection of miR-142-3p mimics into mesothelioma cell lines significantly suppressed ITGAV expression, indicating that miR-142-3p targets ITGAV. Next, ITGAV siRNA transfection into mesothelioma cell lines inhibited cell proliferation, migration, and invasion. Further investigation of cell adhesion mechanisms showed that the miR-142-3p/ITGAV axis specifically affects mesothelioma cell adhesion via vitronectin in the extracellular matrix. Conclusion: This study proposed that the miR-142-3p/ITGAV axis is involved in tumor progression in malignant mesothelioma.

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“…[14][15][16] SPARC expression in tumor-associated stroma is instrumental in tumor survival and progression and serves as a prognostic factor. 14,15,17 In mesothelioma, SPARC is linked to epithelial-mesenchymal transition, 18 and both its expression in tumor stromal cells and blood SPARC levels correlate with prognosis. 19,20 In the current study, SPARC was found to be positive in mesothelioma cells and negative in lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

SPARC Is a Novel Positive Immunohistochemical Marker of Epithelioid Mesothelioma to Differentiate It From Lung Adenocarcinoma and/or Squamous Cell Carcinoma

Nakagiri,

Amatya,

Kushitani

et al. 2023

American Journal of Surgical Pathology

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Epithelioid mesothelioma with a solid histologic pattern (solid epithelioid mesothelioma) is difficult to distinguish from a poorly differentiated squamous cell lung carcinoma and/or solid lung adenocarcinoma. Thus, immunohistochemical markers are essential for diagnosis; however, the sensitivity and specificity of pre-existing mesothelial markers are suboptimal, particularly for differentiation from squamous cell carcinoma. Using a cancer-dependency map, we analyzed gene expression data of pleural mesothelioma and non–small cell lung cancer cell lines (squamous cell carcinoma and adenocarcinoma) and identified secreted protein acidic and cysteine-rich (SPARC) as a promising candidate for the differential diagnosis of epithelioid mesothelioma from lung squamous cell carcinoma and/or lung adenocarcinoma. SPARC expression in mesothelioma and lung cancer cell lines was validated using reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. Immunohistochemical staining was performed using anti-SPARC antibodies against solid epithelioid mesothelioma, solid lung adenocarcinoma, and poorly differentiated lung squamous cell carcinoma. SPARC positivity was seen in 42/45 (93.3%) of solid epithelioid mesothelioma, 2/40 (5%) solid lung adenocarcinoma, and 2/45 (4.5%) of lung squamous cell carcinomas. The sensitivity, specificity, and diagnostic accuracy for differentiating solid epithelioid mesothelioma from lung cancer (solid lung adenocarcinoma and poorly differentiated lung squamous cell carcinoma) were 93.3, 95.2, and 94.6%, respectively. In conclusion, SPARC is a novel mesothelial marker that can be used to differentiate epithelioid mesothelioma from squamous cell carcinoma and lung adenocarcinoma.

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A panel of emerging EMT genes identified in malignant mesothelioma

Cited by 18 publications

References 48 publications

Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial

Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial

miR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV

SPARC Is a Novel Positive Immunohistochemical Marker of Epithelioid Mesothelioma to Differentiate It From Lung Adenocarcinoma and/or Squamous Cell Carcinoma

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