Ribosomal protein S11 influences glioma response to TOP2 poisons

Awah, Chidiebere U.; Chen, Li; Bansal, Mukesh; Mahajan, Aayushi; Winter, J.; Lad, Meeki; Warnke, Louisa; González-Buendía, Edgar; Park, Cheol; Zhang, Daniel Y.; Feldstein, Eric; Yu, Dou; Ζαννίκου, Μαρκέλλα; Balyasnikova, Irina V.; Martuscello, Regina T.; S, Konerman; Győrffy, Balázs; Burdett, Kirsten Bell; Scholtens, Denise M.; Stupp, Roger; Ahmed, Atique U.; Hsu, Patrick; Sonabend, Adam M.

doi:10.1038/s41388-020-1342-0

Cited by 25 publications

(24 citation statements)

References 57 publications

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“…In addition, GESA enrichment analysis showed that ribosome and MYC related signaling pathways are over activated in high-risk patients. Studies have shown that ribosomal protein is abnormally expressed in a variety of tumors, and affects tumor cell apoptosis, senescence, growth, invasion, and drug and radiotherapy resistance through various mechanisms ( Awah et al, 2020 ; Babaian et al, 2020 ). The proliferation of tumor cells is positively correlated with protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

RNA-Binding Proteins CLK1 and POP7 as Biomarkers for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma

Yang

Han

et al. 2021

Front. Cell Dev. Biol.

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The abnormality of RNA-binding proteins (RBPs) is closely related to the tumorigenesis and development of esophageal squamous cell carcinoma (ESCC), and has been an area of interest for research recently. In this study, 162 tumors and 11 normal samples are obtained from The Cancer Genome Atlas database, among which 218 differentially expressed RBPs are screened. Finally, a prognostic model including seven RBPs (CLK1, DDX39A, EEF2, ELAC1, NKRF, POP7, and SMN1) is established. Further analysis reveals that the overall survival (OS) rate of the high-risk group is lower than that of the low-risk group. The area under the receiver operating characteristic (ROC) curve (AUC) of the training group and testing group is significant (AUCs of 3 years are 0.815 and 0.694, respectively, AUCs of 5 years are 0.737 and 0.725, respectively). In addition, a comprehensive analysis of seven identified RBPs shows that most RBPs are related to OS in patients with ESCC, among which EEF2 and ELCA1 are differentially expressed at the protein level of ESCC and control tissues. CLK1 and POP7 expressions in esophageal cancer tumor samples are undertaken using the tissue microarray, and show that CLK1 mRNA levels are relatively lower, and POP7 mRNA levels are higher compared with non-cancerous esophageal tissues. Survival analysis reveals that a higher expression of CLK1 predicts a significant worse prognosis, and a lower expression of POP7 predicts a worse prognosis in esophageal cancer. These results suggest that CLK1 may promote tumor progression, and POP7 may hinder the development of esophageal cancer. In addition, gene set enrichment analysis reveals that abnormal biological processes related to ribosomes and abnormalities in classic tumor signaling pathways such as TGF-β are important driving forces for the occurrence and development of ESCC. Our results provide new insights into the pathogenesis of ESCC, and seven RBPs have potential application value in the clinical prognosis prediction of ESCC.

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Section: Discussionmentioning

confidence: 99%

RNA-Binding Proteins CLK1 and POP7 as Biomarkers for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma

Yang

Han

et al. 2021

Front. Cell Dev. Biol.

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“…Loss of uS17 is associated with acquired resistance to TOP2 poisons. It has been demonstrated that the expression of uS17 was necessary for the induction of apoptosis through apoptotic protease activating factor-1 (APAF1) protein [ 98 ].…”

Section: Rps As Biomarkers In Cancer Diagnosismentioning

confidence: 99%

Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins

Pecoraro

Pagano

Russo

et al. 2021

IJMS

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Cytosolic ribosomes (cytoribosomes) are macromolecular ribonucleoprotein complexes that are assembled from ribosomal RNA and ribosomal proteins, which are essential for protein biosynthesis. Mitochondrial ribosomes (mitoribosomes) perform translation of the proteins essential for the oxidative phosphorylation system. The biogenesis of cytoribosomes and mitoribosomes includes ribosomal RNA processing, modification and binding to ribosomal proteins and is assisted by numerous biogenesis factors. This is a major energy-consuming process in the cell and, therefore, is highly coordinated and sensitive to several cellular stressors. In mitochondria, the regulation of mitoribosome biogenesis is essential for cellular respiration, a process linked to cell growth and proliferation. This review briefly overviews the key stages of cytosolic and mitochondrial ribosome biogenesis; summarizes the main steps of ribosome biogenesis alterations occurring during tumorigenesis, highlighting the changes in the expression level of cytosolic ribosomal proteins (CRPs) and mitochondrial ribosomal proteins (MRPs) in different types of tumors; focuses on the currently available information regarding the extra-ribosomal functions of CRPs and MRPs correlated to cancer; and discusses the role of CRPs and MRPs as biomarkers and/or molecular targets in cancer treatment.

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“…Screening was performed as previously described [14]. H4 human GBM cells were infected with the whole-genome knockout Brunello library (Addgene, Cambridge, MA, USA), which included ~19,000 genes with 4 sgRNAs per gene and 10,000 sgRNA non-targeting controls.…”

Section: Crispr-cas9 Knockout Screeningmentioning

confidence: 99%

ARF4-mediated Retrograde Trafficking Drives Chemoresistance in Glioblastoma

Budhiraja

Baisiwala

Perrault

et al. 2021

Preprint

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Glioblastoma (GBM) is the most common type of adult malignant brain tumor, with a median survival of only 21 months. This is partly due to the high rate of resistance to conventional therapy, including temozolomide (TMZ), leading to recurrence rates close to 100%. It still remains unknown what drives the development of this resistance. To identify the unknown genes driving the development of this resistance, we performed a genome-wide CRISPR knockout screen comparing a DMSO-treated population with a TMZ-treated population over 14 days. We identified 4 previously unstudied genes – ARF4, PLAA, SPTLC1, and PIGK – that showed significant elevations in expression in recurrent tumors in patient datasets, along with significant survival benefits corresponding to low gene expression. Further investigation of ARF4, known to be involved in retrograde trafficking, allowed us to identify a mechanism of resistance that is mediated by increased retrograde transport of EGFR into the nucleus. Ultimately, our CRISPR-Cas9 screen has identified a promising therapeutic target, ARF4, which may drive GBM's high resistance to chemotherapy.

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Ribosomal protein S11 influences glioma response to TOP2 poisons

Cited by 25 publications

References 57 publications

RNA-Binding Proteins CLK1 and POP7 as Biomarkers for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma

RNA-Binding Proteins CLK1 and POP7 as Biomarkers for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma

Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins

ARF4-mediated Retrograde Trafficking Drives Chemoresistance in Glioblastoma

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