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pmid:38523780

RUVBL1 accelerates tongue squamous cell carcinoma by mediating CRaf/MEK/ERK pathway.

Xin-Yu Zhang · Yang Liu · Qiong Rong · Ming-Yue Qi · Hui Guo

iScience · 2024 doi:10.1016/j.isci.2024.109434

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

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RUVBL1 accelerates tongue squamous cell carcinoma by mediating CRaf/MEK/ERK pathway.
doi
10.1016/j.isci.2024.109434
pmid
38523780
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Xin-Yu Zhang
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Yang Liu
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Qiong Rong
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Ming-Yue Qi
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Hui Guo
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iScience
year
2024
abstract
RAF/MEK/ERK pathway is frequently activated in tumor. Therefore, this study will investigate the function of RUVBL1 (RAF-binding protein) in tongue squamous cell carcinoma (TSCC). Bioinformatics was performed to identify differentially expressed mRNAs (DE-mRNAs) in TCGA-oral squamous cell carcinoma, GSE13601, and GSE34105 datasets. A total of 672 shared DE-mRNAs were identified in three datasets, and they are regulating metastasis and angiogenesis. Patients with RUVBL1 low expression had high overall survival. Overexpressing RUVBL1 enhanced the viability, wound healing percentage, invasion, sphere formation, angiogenesis, and resistance to cisplatin and 5-fluorouracil in CAL-27 and SCC-4 cells, and the opposite results were obtained by knocking down RUVBL1. Moreover, overexpression of RUVBL1 bolstered tumor growth in vivo. Strikingly, RUVBL1 diminished the phosphorylation of CRAF Ser259, which led to activation of the MEK/ERK pathway. In conclusion, RUVBL1 contributes to the malignant biological behavior of TSCC via activating the CRAF/MEK/ERK pathway. This provides molecular mechanisms and perspectives for targeted therapy of the CRAF/MEK/ERK pathway.
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The differential expression analysis for the GSE13601 and GSE34105 datasets was performed based on the limma package,42 while the TCGA-OSCC dataset was performed based on the DESeq package.43 The thresholds for differentially expressed mRNAs (DE-mRNAs) satisfy both adj. p < 0.05 and |log2FC|>0.5.
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The differential expression analysis for the GSE13601 and GSE34105 datasets was performed based on the limma package,42 while the TCGA-OSCC dataset was performed based on the DESeq package.43 The thresholds for differentially expressed mRNAs (DE-mRNAs) satisfy both adj. p < 0.05 and |log2FC|>0.5.
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Log rank test based on the TCGA dataset displayed that TSCC patients with high expression of RUVBL1 had a lower overall survival than those with low expression of RUVBL1, and both were statistically significant (Figure 1E, p = 0.024).
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Log rank test based on the TCGA dataset displayed that TSCC patients with high expression of RUVBL1 had a lower overall survival than those with low expression of RUVBL1, and both were statistically significant (Figure 1E, p = 0.024).
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Log rank test based on the TCGA dataset displayed that TSCC patients with high expression of RUVBL1 had a lower overall survival than those with low expression of RUVBL1, and both were statistically significant (Figure 1E, p = 0.024).
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Log rank test based on the TCGA dataset displayed that TSCC patients with high expression of RUVBL1 had a lower overall survival than those with low expression of RUVBL1, and both were statistically significant (Figure 1E, p = 0.024).
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The differential expression analysis for the GSE13601 and GSE34105 datasets was performed based on the limma package,42 while the TCGA-OSCC dataset was performed based on the DESeq package.43 The thresholds for differentially expressed mRNAs (DE-mRNAs) satisfy both adj. p < 0.05 and |log2FC|>0.5.
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rexpression of RUVBL1 bolstered tumor growth in vivo. Strikingly, RUVBL1 diminished the phosphory
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Bioinformatics was performed to identify differentially expressed mRNAs (DE-mRNAs) in TCGA-oral squamous cell carcinoma, GSE13601, and GSE34105 datasets. A total of 672 shared DE-mRNAs were identified in three datasets, and they are regulating metastasis and angiogenesis. Patients with RUVBL1 low expression had high overall survival. Overexpressing RUVBL1 enhanced the viability, wound healing percentage, invasion, sphere formation, angiogenesis, and resistance to cisplatin and 5-fluorouracil in CAL-27 and SCC-4 cells, and the opposite results were obtained by knocking down RUVBL1. Moreover, overexpression of RUVBL1 bolstered tumor growth in vivo. Strikingly, RUVBL1 diminished the phosphorylation of CRAF Ser259, which led to activation of the MEK/ERK pathway. In conclusion, RUVBL1 contributes to the malignant biological behavior of TSCC via activating the CRAF/MEK/ERK pathway. 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