YBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA

Kloetgen, Andreas; Duggimpudi, Sujitha; Schuschel, Konstantin; Hezaveh, Kebria; Picard, Daniel; Schaal, Heiner; Remke, Marc; Klusmann, Jan‐Henning; McHardy, Alice C.; Hoell, Jessica I.

doi:10.3390/ijms21124453

Cited by 15 publications

(13 citation statements)

References 65 publications

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“…Notably, NDRG1 is subjected to post-transcriptional gene silencing upon Influenza A infection [82]. The RNA stability of the chromatinrelated gene CBX5/HP1 has also been linked to the inflammatory response and apoptosis [83]. The chromatin disorganization suffered upon CBX5 deregulation has been proposed to modulate lung tumor progression [84] as well as the infection by HIV [85][86][87].…”

Section: Discussionmentioning

confidence: 99%

Novel SARS-CoV-2 encoded small RNAs in the passage to humans

et al. 2020

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Motivation The Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) has recently emerged as the responsible for the pandemic outbreak of the coronavirus disease (COVID-19). This virus is closely related to coronaviruses infecting bats and Malayan pangolins, species suspected to be an intermediate host in the passage to humans. Several genomic mutations affecting viral proteins have been identified, contributing to the understanding of the recent animal-to-human transmission. However, the capacity of SARS-CoV-2 to encode functional putative microRNAs (miRNAs) remains largely unexplored. Results We have used deep learning to discover 12 candidate stem-loop structures hidden in the viral protein-coding genome. Among the precursors, the expression of eight mature miRNAs-like sequences was confirmed in small RNA-seq data from SARS-CoV-2 infected human cells. Predicted miRNAs are likely to target a subset of human genes of which 109 are transcriptionally deregulated upon infection. Remarkably, 28 of those genes potentially targeted by SARS-CoV-2 miRNAs are down-regulated in infected human cells. Interestingly, most of them have been related to respiratory diseases and viral infection, including several afflictions previously associated with SARS-CoV-1 and SARS-CoV-2. The comparison of SARS-CoV-2 pre-miRNA sequences with those from bat and pangolin coronaviruses suggests that single nucleotide mutations could have helped its progenitors jumping inter-species boundaries, allowing the gain of novel mature miRNAs targeting human mRNAs. Our results suggest that the recent acquisition of novel miRNAs-like sequences in the SARS-CoV-2 genome may have contributed to modulate the transcriptional reprogramming of the new host upon infection.

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Section: Discussionmentioning

confidence: 99%

Novel SARS-CoV-2 encoded small RNAs in the passage to humans

et al. 2020

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“…Despite considerable research in solid tumors, there is a significant lack of studies exploring the role of YB-1 in pediatric brain tumors or indeed in brain and CNS tumors in general. Elevated YBX1 expression has been reported in both pGBM and MB (19,28,29). Further, analysis of large-scale, publically available datasets shows YBX1 expression is substantially increased not only in MB and pGBM, but also in DIPG, anaplastic astrocytoma and ependymoma (Figure 1A).…”

Section: Yb-1 In Brain Tumors -A Neglected Therapeutic Target?mentioning

confidence: 85%

“…There is evidence to support the use of YB-1 as a prognostic biomarker in pediatric brain tumors. Analysis of patient data demonstrates that YBX1 mRNA is up-regulated in MB and high-grade pediatric glioma where it correlates with poor survival outcome (Figure 1A-C) (19,28,29). Indeed, a number of studies have proposed YB-1 as a novel biomarker of glioma progression.…”

Section: Yb-1 As a Biomarkermentioning

confidence: 99%

Y-Box Binding Protein-1: A Neglected Target in Pediatric Brain Tumors?

Taylor

Kerr

Coyle

2021

Molecular Cancer Research

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Brain and central nervous system (CNS) tumors represent the most common childhood solid tumors. Comprising 21% of all pediatric cancers, they remain the leading cause of cancer-related mortality and morbidity in childhood. Due to advances in neurosurgical technique, radiation therapy and the use of combination therapy, survival rates have generally increased. However, by cause of the lesion itself, its surgical removal and subsequent treatment, survivors are at high risk of long-term neurocognitive sequelae and secondary cancer. Clearly, improvements in diagnosis and treatment are needed. Accordingly, current treatment is evolving away from conventional, uniform therapy and towards risk-stratified regimens and molecularlytargeted therapies, with the aim of diminishing adverse side effects while minimising the risk of disease recurrence. The multi-functional oncoprotein Y-box binding protein 1 (YB-1) may serve as one such molecular target. Increased YB-1 levels have been reported in a number of pediatric brain tumors, where YB-1 appears to facilitate the advancement of malignant phenotypes. These include proliferation, invasion and resistance to therapy, as well as the maintenance of brain tumor initiating cells. Here we evaluate the current literature and show how YB-1 modulates signalling pathways driving each of these phenotypes. We also review the regulation of YB-1 at a transcriptional, translational, post-translational and sub-cellular level and argue that there is strong and sufficient evidence to support the development of YB-1 as a biomarker and future therapeutic target in childhood brain tumors.

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“…We additionally studied the mechanisms whereby YBX1 may promote tumor progression in the present study. In prior reports, the RRM2/TK1/TYMS axis has been found to regulate nucleotide metabolism and to govern the proliferation and senescence of tumor cells [26]. YBX1 induces the proliferation of cells via promoting GSK3B/Cyclin D1/Cyclin E1 pathway activation in pancreatic ductal adenocarcinoma [27], and drives renal cell carcinoma metastasis through the G3BP1-SPP1-NF-κB signaling pathway [28].…”

Section: Discussionmentioning

confidence: 96%

YBX1 promotes laryngeal squamous cell carcinoma progression via activating MAPK/ERK signaling as a target of miR-382-5p

Zeng¹,

Pan²,

Luo

et al. 2021

Preprint

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Background. Y-box binding protein-1 (YBX1) influences the onset and progression of laryngeal squamous cell carcinoma (LSCC) remains unknown. The present study therefore sought to explore the mechanistic role of YBX1 in LSCC. Methods.Analyses of the Gene Expression Omnibus (GEO) database and associated bioinformatics analyses revealed that YBX1 was upregulated in LSCC, and we further confirmed this result using primary LSCC patient samples. We additionally explored the impact of siRNA-mediated YBX1 knockdown on LSCC cell proliferation, migration, and invasion using CCK8, wound healing, and Transwell assays. We then conducted interrogated miRNA databases and conducted subsequent luciferase reporter assays to confirm that miR-382-5p binds to YBX1. Additional studies of the mechanisms downstream of this miR-382-5p/YBX1 axis focused on detecting the expression of mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK) signaling-related genes via qPCR and Western blotting. Results.We detected significant upregulation of YBX1 in LSCC tumors that was significantly correlated with advanced TNM stage and poor patient prognosis. Knockdown of YBX1 markedly impaired the proliferative, invasive, and migratory activity of Tu212 cells in vitro. From a mechanistic perspective, miR-382-5p was found to bind to the YBX1 3’-untranslated region and to thereby inhibit LSCC progression. We further confirmed that miR-382-5p negatively regulated YBX1 to inhibit proliferation via the MAPK/ ERK signaling axis in LSCC. Conclusion.Together, our results indicated that YBX1 is an important promoter of LSCC progression, and that miR-382-5p can suppress YBX1 expression and inactivate MAPK/ERK signaling. These findings may thus highlight novel and promising prognostic and therapeutic targets in the context of LSCC.

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YBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA

Cited by 15 publications

References 65 publications

Novel SARS-CoV-2 encoded small RNAs in the passage to humans

Novel SARS-CoV-2 encoded small RNAs in the passage to humans

Y-Box Binding Protein-1: A Neglected Target in Pediatric Brain Tumors?

YBX1 promotes laryngeal squamous cell carcinoma progression via activating MAPK/ERK signaling as a target of miR-382-5p

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