Fibronectin protein expression in renal cell carcinoma in correlation with clinical stage of tumour

Kondisetty, Sandeep; Menon, Krishnakumar N.; Pooleri, Ginil Kumar

doi:10.1186/s40364-018-0137-8

Cited by 7 publications

(8 citation statements)

References 15 publications

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“…The regulation of cell proliferation and migration is multifactorial. Studies have highlighted the crucial role of fibronectin in RCC cell proliferation and motility, and have demonstrated its prognostic value [8,10,11,12,13,14,15,16,17]. Using 786-O and Caki-1 cells with fibronectin silencing, the results of our study further emphasize the importance and crucial role of fibronectin, Src, and TGF-β1/Smad in the regulation of RCC cell growth and migration.…”

Section: Discussionsupporting

confidence: 66%

“…Fibronectin is upregulated in RCC and is therefore of prognostic value. Moreover, it has been shown to be a promising biomarker for therapeutic responses [8,10,11,12,13,14,15,16,17]. In this study, manipulation of cellular fibronectin expression by RNAi and exogenous additions altered cellular activities and intracellular signaling in RCC 786-O and Caki-1 cells.…”

Section: Discussionmentioning

confidence: 73%

“…Accumulating evidence has indicated its carcinogenic and malignant role in several malignancies [5,6,7,8,9]. In RCC, tissue and plasma levels of fibronectin are elevated in the advanced stages, and thus fibronectin appears to be a promising biomarker for therapeutic responses [8,10,11,12,13,14,15,16,17]. Although data from clinical and experimental studies highlight the role of fibronectin in RCC prognosis and acquisition of RCC malignancy, the underlying molecular and biochemical basis of fibronectin in promoting malignant progression of RCC remain incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

“…However, our current understanding of cellular events in fibronectin-promoted RCC cell growth and migration is limited. Since fibronectin overexpression in RCC has been strongly associated with advanced clinical stages, metastases, and poor survival [8,14,16,17], the aim of the current study was to investigate the intracellular signaling events critical to fibronectin-promoted cell growth and migration.…”

Section: Introductionmentioning

confidence: 99%

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Fibronectin Promotes Cell Growth and Migration in Human Renal Cell Carcinoma Cells

Wang

et al. 2019

IJMS

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The prognostic and therapeutic values of fibronectin have been reported in patients with renal cell carcinoma (RCC). However, the underlying mechanisms of malignancy in RCC are not completely understood. We found that silencing of fibronectin expression attenuated human RCC 786-O and Caki-1 cell growth and migration. Silencing of potential fibronectin receptor integrin α5 and integrin β1 decreased 786-O cell ability in movement and chemotactic migration. Biochemical examination revealed a reduction of cyclin D1 and vimentin expression, transforming growth factor-β1 (TGF-β1) production, as well as Src and Smad phosphorylation in fibronectin-silenced 786-O and Caki-1 cells. Pharmacological inhibition of Src decreased 786-O cell growth and migration accompanied by a reduction of cyclin D1, fibronectin, vimentin, and TGF-β1 expression, as well as Src and Smad phosphorylation. In 786-O cells, higher activities in cell growth and migration than in Caki-1 cells were noted, along with elevated fibronectin and TGF-β1 expression. The additions of exogenous fibronectin and TGF-β1 promoted Caki-1 cell growth and migration, and increased cyclin D1, fibronectin, vimentin, and TGF-β1 expression, as well as Src and Smad phosphorylation. These findings highlight the role of fibronectin in RCC cell growth and migration involving Src and TGF-β1 signaling.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fibronectin Promotes Cell Growth and Migration in Human Renal Cell Carcinoma Cells

Wang

et al. 2019

IJMS

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“…In recent years, Fibronectin 1 has been gradually certified as an oncogene, which regulates metastasis in various cancers include RCC. It is also one of the main functional markers and regulatory factors of EMT 61. Through cell transfection and luciferase reporter assays, it was also confirmed that Fibronectin 1 was a direct target gene of miR-1-3p.…”

Section: Discussionmentioning

confidence: 76%

<p>miR-1-3p suppresses the epithelial-mesenchymal transition property in renal cell cancer by downregulating Fibronectin 1</p>

Liu¹,

Huang²,

Cheng³

et al. 2019

CMAR

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Purpose Renal cell cancer (RCC) is one of the primary causes of malignancy deaths all over the world. The most important cause of RCC-related mortality is metastasis. Epithelial-mesenchymal transition (EMT) plays an important role in metastasis of malignant tumors including RCC. miR-1-3p is confirmed to be decreased in many types of cancer. Nevertheless, the function of miR-1-3p in RCC metastasis and EMT process was still unclear. Materials and methods In this study, information from clinical investigation, in vitro study, and in vivo study discovered miR-1-3p expression character and its status in RCC. The character of miR-1-3p in invasive and metastatic properties in vitro and in vivo was also inspected in RCC cells and xenograft tumor model, and expression levels of EMT markers were evaluated in RCC cells and tissues. Results miR-1-3p was proved to be decreased in RCC cell lines and tissues compared with normal renal cells and tissues. miR-1-3p expression level in RCC tissues was closely related with capsulation, lymph node metastasis, and vascular invasion. miR-1-3p was found to be able to block the EMT process in A498 and CAKI-1 RCC cells and tumors. Luciferase reporter assay and expression level rescue assays were employed to reveal that miR-1-3p inhibited the invasion and migration property of RCC cells by directly targeting Fibronectin 1. Upregulation of Fibronectin 1 partially reversed the suppressive effect of miR-1-3p on EMT process. Conclusion In brief, this study has verified that miR-1-3p blocked the EMT process of RCC cells by reducing Fibronectin 1 expression. miR-1-3p/Fibronectin 1 axis may be considered as a new target for drug development of RCC.

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Identification of C3 and FN1 as potential biomarkers associated with progression and prognosis for clear cell renal cell carcinoma

Dong

Yang

et al. 2021

BMC Cancer

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Background Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urological malignancies, but the pathogenesis and prognosis of ccRCC remain obscure, which need to be better understand. Methods Differentially expressed genes were identified and function enrichment analyses were performed using three publicly available ccRCC gene expression profiles downloaded from the Gene Expression Omnibus database. The protein-protein interaction and the competing endogenous RNA (ceRNA) networks were visualized by Cytoscape. Multivariate Cox analysis was used to predict an optimal risk mode, and the survival analysis was performed with the Kaplan-Meier curve and log-rank test. Protein expression data were downloaded from Clinical Proteomic Tumor Analysis Consortium database and Human Protein Atlas database, and the clinical information as well as the corresponding lncRNA and miRNA expression data were obtained via The Cancer Genome Atlas database. The co-expressed genes and potential function of candidate genes were explored using data exacted from the Cancer Cell Line Encyclopedia database. Results Of the 1044 differentially expressed genes shared across the three datasets, 461 were upregulated, and 583 were downregulated, which significantly enriched in multiple immunoregulatory-related biological process and tumor-associated pathways, such as HIF-1, PI3K-AKT, P53 and Rap1 signaling pathways. In the most significant module, 36 hub genes were identified and were predominantly enriched in inflammatory response and immune and biotic stimulus pathways. Survival analysis and validation of the hub genes at the mRNA and protein expression levels suggested that these genes, particularly complement component 3 (C3) and fibronectin 1 (FN1), were primarily responsible for ccRCC tumorigenesis and progression. Increased expression of C3 or FN1 was also associated with advanced clinical stage, high pathological grade, and poor survival in patients with ccRCC. Univariate and multivariate Cox regression analysis qualified the expression levels of the two genes as candidate biomarkers for predicting poor survival. FN1 was potentially regulated by miR-429, miR-216b and miR-217, and constructed a bridge to C3 and C3AR1 in the ceRNA network, indicating a critical position of FN1. Conclusions The biomarkers C3 and FN1 could provide theoretical support for the development of a novel prognostic tool to advance ccRCC diagnosis and targeted therapy.

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Fibronectin protein expression in renal cell carcinoma in correlation with clinical stage of tumour

Cited by 7 publications

References 15 publications

Fibronectin Promotes Cell Growth and Migration in Human Renal Cell Carcinoma Cells

Fibronectin Promotes Cell Growth and Migration in Human Renal Cell Carcinoma Cells

<p>miR-1-3p suppresses the epithelial-mesenchymal transition property in renal cell cancer by downregulating Fibronectin 1</p>

Identification of C3 and FN1 as potential biomarkers associated with progression and prognosis for clear cell renal cell carcinoma

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