FXYD5/Dysadherin, a Biomarker of Endometrial Cancer Myometrial Invasion and Aggressiveness: Its Relationship With TGF-β1 and NF-κB Pathways

Besso, María José; Rosso, Marina; Lapyckyj, Lara; Moiola, Cristian P.; Matos, Matheus J. S.; Mercogliano, María F.; Schillaci, Roxana; Reventós, Jaume; Colás, Eva; Wernicke, Alejandra; Orti, R.; Vazquez‐Levin, Mónica H.

doi:10.3389/fonc.2019.01306

Cited by 16 publications

(16 citation statements)

References 44 publications

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“…Similarly, biological experiments in vitro and in vivo showed that FXYD5 promoted the metastasis of ovarian cancer cells via TGF-β/SMAD signaling pathways [39]. Besides, a study demonstrated that FXYD5/Dys could serve as a biomarker of endometrial cancer progression associated with TGF-β1 and NF-κB signaling pathways [40]. The findings from the present study confirmed the reliability and accuracy of hub genes as prognostic biomarkers in tumors, particularly in meningiomas.…”

Section: Discussionsupporting

confidence: 81%

Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis

Yang

Wei

et al. 2020

BioMed Research International

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Meningiomas are the most common primary intracranial tumor in adults. However, to date, systemic coexpression analyses for meningiomas fail to explain its pathogenesis. The aim of the present study was to construct coexpression modules and identify potential biomarkers associated with meningioma progression. Weighted gene coexpression network analysis (WGCNA) was performed based on GSE43290, and module preservation was tested by GSE74385. Functional annotations were performed to analyze biological significance. Hub genes were selected for efficacy evaluations and correlation analyses using two independent cohorts. A total of 14 coexpression modules were identified, and module lightcyan was significantly associated with WHO grades. Functional enrichment analyses of module lightcyan were associated with tumor pathogenesis. The top 10 hub genes were extracted. Ten biomarkers, particularly AHCYL2, FGL2, and KCNMA1, were significantly related to grades and prognosis of meningioma. These findings not only construct coexpression modules leading to the better understanding of its pathogenesis but also provide potential biomarkers that represent specific on tumor grades and identify recurrence, predicting prognosis and progression of meningiomas.

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Section: Discussionsupporting

confidence: 81%

Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis

Yang

Wei

et al. 2020

BioMed Research International

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“…Based on previous studies ( 29 – 31 ), the gene regulatory network of CDK8 was analyzed and identified using GENEVESTIGATOR ® ( ).…”

Section: Methodsmentioning

confidence: 99%

miR‑592 acts as an oncogene and promotes medullary thyroid cancer tumorigenesis by targeting cyclin‑dependent kinase 8

2020

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Medullary thyroid carcinoma (MTC) is a relatively rare subtype of thyroid cancer, accounting for 5–10% of all cases of thyroid cancer worldwide. Due to the current lack of knowledge regarding the tumorigenesis of MTC, the clinical treatment of MTC remains a challenge. It has been reported that microRNAs (miRNAs) regulate the progression of MTC; however, the regulatory network of miRNAs and the exact underlying mechanisms are not completely understood. In the present study, an miRNA expression profile (GSE40807), consisting of 80 samples, was downloaded and analyzed using Gene Expression Omnibus-2R to identify differentially expressed miRNAs between MTC and normal samples. miR-592 expression levels were significantly increased in MTC tissues and cell lines compared with normal tissues and cell lines. Patients with high miR-592 expression levels exhibited a less favorable prognosis compared with patients with low miR-592 expression. The results suggested that miR-592 overexpression promoted TT and MZ-CRC-1 cell proliferation in vitro . In addition, miR-592 negatively regulated cyclin-dependent kinase 8 (CDK8) via targeted binding in MTC cells. Moreover, co-transfection of CDK8 overexpression plasmid and miR-592 mimic reversed miR-592-mediated MTC cell proliferation. In conclusion, miR-592 may serve as an oncogene in MTC by decreasing the expression of CDK8, indicating that the miR-592/CDK8 axis might serve as a promising therapeutic target for MTC.

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“…FXYD5 also disperses the TβR1 complex leading to enhanced TGF-β signalling and SMAD3/4 activation, which in turn upregulates FXYD5 gene expression in ovarian cancer 58 . In line, TGF-β treatment induced FXYD5 expression in endometrial cancer, which in turn led to activation of NF-κβ pathway 59 . Furthermore, in breast cancer cell lines, high FXYD5 expression correlates with activation of AKT signalling, which drives the EMT 60 .…”

Section: Discussionmentioning

confidence: 83%

MMP8 increases tongue carcinoma cell–cell adhesion and diminishes migration via cleavage of anti-adhesive FXYD5

et al. 2021

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Matrix metalloproteinases (MMPs) modify bioactive factors via selective processing or degradation resulting in tumour-promoting or tumour-suppressive effects, such as those by MMP8 in various cancers. We mapped the substrates of MMP8 to elucidate its previously shown tumour-protective role in oral tongue squamous cell carcinoma (OTSCC). MMP8 overexpressing (+) HSC-3 cells, previously demonstrated to have reduced migration and invasion, showed enhanced cell-cell adhesion. By analysing the secretomes of MMP8 + and control cells with terminal amine isotopic labelling of substrates (TAILS) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS), we identified 36 potential substrates of MMP8, including FXYD domain-containing ion transport regulator 5 (FXYD5). An anti-adhesive glycoprotein FXYD5 has been previously shown to predict poor survival in OTSCC. Cleavage of FXYD5 by MMP8 was confirmed using recombinant proteins. Furthermore, we detected a loss of FXYD5 levels on cell membrane of MMP8 + cells, which was rescued by inhibition of the proteolytic activity of MMP8. Silencing (si) FXYD5 increased the cell-cell adhesion of control but not that of MMP8 + cells. siFXYD5 diminished the viability and motility of HSC-3 cells independent of MMP8 and similar effects were seen in another tongue cancer cell line, SCC-25. FXYD5 is a novel substrate of MMP8 and reducing FXYD5 levels either with siRNA or cleavage by MMP8 increases cell adhesion leading to reduced motility. FXYD5 being a known prognostic factor in OTSCC, our findings strengthen its potential as a therapeutic target.

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FXYD5/Dysadherin, a Biomarker of Endometrial Cancer Myometrial Invasion and Aggressiveness: Its Relationship With TGF-β1 and NF-κB Pathways

Cited by 16 publications

References 44 publications

Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis

Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis

miR‑592 acts as an oncogene and promotes medullary thyroid cancer tumorigenesis by targeting cyclin‑dependent kinase 8

MMP8 increases tongue carcinoma cell–cell adhesion and diminishes migration via cleavage of anti-adhesive FXYD5

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