Abstract
BackgroundEPB41L1 gene (erythrocyte membrane protein band 4.1 like 1) encodes the protein 4.1N, a member of 4.1 family, playing a vital role in cell adhesion and migration, which is associated with the malignant progression of various human cancers. However, the expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma (KIRC) remain to be investigated.MethodsIn this study, we collected the mRNA expression of EPB41L1 in KIRC through the Oncomine platform, and used the HPA database to perform the pathological tissue immunohistochemistry in patients. Then, the sub-groups and prognosis of KIRC were performed by UALCAN and GEPIA web-tool, respectively. Further, the mutation of EPB41L1 in KIRC was analyzed by c-Bioportal. The co-expression genes of EPB41L1 in KIRC were displayed from the LinkedOmics database, and function enrichment analysis was used by LinkFinder module in LinkedOmics. The function of EPB41L1 in cell adhesion and migration was confirmed by wound healing assay using 786-O cells in vitro. Co-expression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules, both of them was visualized by Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in TCGA by using the UCSC Xena browser.ResultsThe results indicated that EPB41L1 was down-expressed in KIRC, leading to a poor prognosis. Moreover, there is a mutation in the FERM domain of EPB41L1, but it has no significant effect on the prognosis of KIRC. The co-expressed genes of EPB41L1 were associated with cell adhesion and confirmed in vitro. Further analysis suggested that EPB41L1 and amyloid beta precursor protein (APP) were coordinated to regulated cancer cell adhesion, thereby increasing the incidence of cancer cell metastasis and tumor invasion.ConclusionsIn summary, EPB41L1 is constantly down-expressed in KIRC tissues, resulting a poor prognosis. Therefore, we suggest that it can be an effective biomarker for the diagnosis of KIRC.
Highlights
Erythrocyte membrane protein band 4.1 like 1 (EPB41L1) gene encodes the protein 4.1N, a member of 4.1 family, playing a vital role in cell adhesion and migration, which is associated with the malignant progression of various human cancers
Expression of EPB41L1 in human kidney renal clear cell carcinoma (KIRC) Firstly, we analyzed the transcription levels of EPB41L1 in KIRC tumors from a series of studies linked to the Oncomine database and found that the mRNA expression of EPB41L1 in KIRC tissues was obviously lower compared to normal tissues (P 0.05)
EPB41L1 expression in subtype of human KIRC To further prove the specificity of EPB41L1 in KIRC, we integrated various clinic factors of KIRC samples in the The Cancer Genome Atlas (TCGA) database, for example, cancer stages, tumor grade, KIRC subtype, nodal metastasis status, patients’ gender, and age, and to compare the transcription levels of EPB41L1 in each group
Summary
EPB41L1 gene (erythrocyte membrane protein band 4.1 like 1) encodes the protein 4.1N, a member of 4.1 family, playing a vital role in cell adhesion and migration, which is associated with the malignant progression of various human cancers. The expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma (KIRC) remain to be investigated. Kidney Renal Clear Cell Carcinoma (KIRC) is the most common subpopulation of kidney cancer [1] and is derived from the proximal uriniferous tubules, often displays an aggressive phenotype, including metastases to. Just like other protein 4.1 family members, 4.1N as a bridge connecting actin cytoskeleton and various transmembrane proteins plays a key role in cell invasion, migration, and adhesion [8]. The previous study has shown that 4.1N associated with the cell adhesion molecule CADM1 expresses in distal tubules. The role of 4.1N in KIRC remains to be fully elucidated
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