Dataset Information

Agrin has a pathological role in the progression of oral cancer.

ABSTRACT: BACKGROUND:The extracellular matrix modulates the hallmarks of cancer. Here we examined the role of agrin-a member of this matrix-in progression of oral squamous cell carcinoma (OSCC). METHODS:We evaluated the immunohistochemical expression of agrin in OSCC and dysplasias. Benign lesions were used as control. In subsequent experiments, we investigated whether the silencing of agrin interferes with tumour expansion both in vitro as well as in vivo. To gain insights into the role of agrin, we identified its protein network (interactome) using mass spectrometry-based proteomics and bioinformatics. Finally, we evaluated the clinical relevance of agrin interactome. RESULTS:Agrin was elevated in malignant and premalignant lesions. Further, we show that agrin silencing interferes with cancer cell motility, proliferation, invasion, colony and tumour spheroid formation, and it also reduces the phosphorylation of FAK, ERK and cyclin D1 proteins in OSCC cells. In orthotopic model, agrin silencing reduces tumour aggressiveness, like vascular and neural invasion. From a clinical perspective, agrin contextual hubs predict a poor clinical prognosis related with overall survival. CONCLUSIONS:Altogether, our results demonstrate that agrin is a histological marker for the progression of oral cancer and is a strong therapeutic target candidate for both premalignant and OSCC lesions.

SUBMITTER: Rivera C

PROVIDER: S-EPMC6008410 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Agrin has a pathological role in the progression of oral cancer.

Rivera César C Zandonadi Flávia Silva FS Sánchez-Romero Celeste C Soares Ciro Dantas CD Granato Daniela Campos DC González-Arriagada Wilfredo Alejandro WA Paes Leme Adriana Franco AF

British journal of cancer 20180606 12

<h4>Background</h4>The extracellular matrix modulates the hallmarks of cancer. Here we examined the role of agrin-a member of this matrix-in progression of oral squamous cell carcinoma (OSCC).<h4>Methods</h4>We evaluated the immunohistochemical expression of agrin in OSCC and dysplasias. Benign lesions were used as control. In subsequent experiments, we investigated whether the silencing of agrin interferes with tumour expansion both in vitro as well as in vivo. To gain insights into the role of ...[more]

PMID: 29872149

Similar Datasets

Project description:Differential expression of non-coding RNA after traumatic spinal cord injury (TSCI) is closely related to the pathophysiological process. The purposes of this study were to systematically profile and characterize expression of circular RNA (circRNA) in the lesion epicenter of spinal tissues after TSCI, and predict the structure and potential function of the regulatory circRNA/miRNA network. Forty-eight C57BL/6 mice were randomly and equally assigned to two groups: one subjected to TSCI at T8-10 with an Allen's drop impactor, and a second subjected to laminectomy without TSCI. Spinal cord samples were stained with hematoxylin and eosin, sequenced, and validated. RNA-Seq, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and network analyses (Targetscan and miRanda) were used to predict and annotate the circRNA/miRNA/mRNA network. Luciferase reporter, quantitative reverse transcription polymerase chain reaction, and western blot assays were used to profile expression and regulation patterns of the network in mouse models of TSCI. Hematoxylin-eosin staining revealed severe damage to the blood-spinal cord barrier after TSCI. Differentially expressed circRNA and miRNA profiles were obtained after TSCI; differentially expressed circRNAs, which were abundant in the cytoplasm, were involved in positive regulation of transcription and protein phosphorylation. miR-135b-5p was the most significantly downregulated miRNA after TSCI; circRNAAbca1 and KLF4 were predicted to be its target circRNA and mRNA, respectively. Subsequently, the circAbca1/miR-135b-5P/KLF4 regulatory axis was predicted and constructed, and its targeted binding was verified. After inhibiting circAbca1, GAP43 expression was upregulated. Differential expression of circRNAs might play an important role after TSCI. circAbca1 plays a neuroinhibitory role by targeted binding of the miR-135b-5P/KLF4 axis. The identified circRNA/miRNA/mRNA network could provide the basis for understanding pathophysiological mechanisms underlying TSCI, as well as guide the formulation of related therapeutic strategies. All animal protocols were approved by the Research Ethics Committee of West China Hospital of China (approval No. 2017128) on May 16, 2017.

Project description:Background: Evidence suggest periodontal bacterial infection can contribute to oral cancer initiation and progression. Aim: To investigate the effects of periodontal bacteria on oral cancer cell behavior using a cell-based system and a mouse carcinogenesis model. Methods: Oral cancer cell lines were polyinfected with four periodontal bacteria. Cytokine levels and relative changes in oncogene mRNA expression were determined post-infection. Oral tumours in mice induced by 4-nitroquinoline-1-oxide (4NQO) were compared with and without administrating periodontal bacteria. Results: Polyinfected oral cancer cells had upregulated MMP1, MMP9, and IL-8. The expression of cell survival markers MYC, JAK1, and STAT3 and epithelial-mesenchymal transition markers ZEB1 and TGF-β were also significantly elevated. Monoinfections showed F. nucleatum alone had comparable or greater effects than the four bacteria together. Fusobacterial culture supernatant, primarily LPS, was sufficient to induce IL-8 secretion, demonstrating that direct contact of live Fusobacteria with cancer cells might not be required to exert changes in cancer cell behaviour. In the 4NQO-induced oral tumour model, mice infected with bacteria developed significantly larger and more numerous lesions compared to those not infected. Conclusion: This study demonstrated that Fusobacteria could potentially enhance cancer cell invasiveness, survival, and EMT when presented in the oral tumour microenvironment. Abbreviations: 4NQO, 4-nitroquinoline-1-oxide; ELISA, enzyme-linked immunosorbent assay; EMT, epithelial-mesenchymal transition; IL-8, interleukin-8; JAK1, Janus kinase 1; LPS, lipopolysaccharide; MMP, matrix metalloproteinase; OSCCs, oral squamous cell carcinomas; PK, proteinase K; PMB, Polymyxin B; qRT-PCR, quantitative real-time polymerase chain reaction; STAT3, signal transducer and activator of transcription 3; TGF-β, transforming growth factor beta; ZEB1, zinc finger E-Box binding homeobox 1.

Dataset Information

Agrin has a pathological role in the progression of oral cancer.

Publications

Agrin has a pathological role in the progression of oral cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets