The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia

Hoang, Van T.; Verma, Divij; Godavarthy, Parimala Sonika; Llavona, Pablo; Steiner, Marlene; Gerlach, Katharina; Michels, Birgitta E.; Bohnenberger, Hanibal; Wachter, Astrid; Oellerich, Thomas; Müller-Kuller, Uta; Weissenberger, Eva; Voutsinas, Jenna; Farin, Henner F.; Zörnig, Martin; Krause, Daniela

doi:10.1038/s41375-018-0358-8

Cited by 16 publications

(22 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although three nuclear localization signals (NLS) confers the enrichment of Fubp1 in the nucleus [ 2 ], Fubp1 could translocate to the cytoplasm under various stimuli including viral infection and apoptosis to control mRNA stability or translation of its target genes [ 3 , 4 ]. Increasing evidence has demonstrated the oncogenic role of Fubp1 and deregulated expression of FUBP1 has been reported in several types of tumors, including hepatocellular carcinoma [ 5 , 6 ], nasopharyngeal carcinoma [ 7 ], gastric cancer [ 8 ], leukemia [ 9 ] and neuroblastoma [ 10 ]. The molecular mechanisms by which FUBP1 contributes to tumor propagation are currently being investigated.…”

Section: Introductionmentioning

confidence: 99%

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Kang

Kim

et al. 2020

Cells

View full text Add to dashboard Cite

The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named “double-agent” genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 “double-agent” genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels of Ccna genes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development.

show abstract

Section: Introductionmentioning

confidence: 99%

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Kang

Kim

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…We further illustrate how PaDETO detects samples that were intentionally switched by us ( Figure S3 ). Last, we show that PaDETO was able to detect an outlier sample ( Figure 4A ) that was not detected originally using manual PCA interpretation (18), thus leading to an improved analysis and conclusions (see below). Taking together, we concluded that PaDETO is a powerful algorithm to identify discrepancies in the data, which improves regular PCA interpretation when it is hard to consider all mathematical aspects.…”

Section: Resultsmentioning

confidence: 79%

“…To test whether BiSEK can improve findings from RNA-seq data that were also tested experimentally, we concentrated on data from CML cells of Mice bone marrow (BM) from a recent paper by (18). Hoang et al used the standard DESeq2 pipeline to test the impact of Far Upstream Element Binding Protein 1 (FUBP1) in CML Leukemia, by comparing between the RNA expression of mice that were transplanted with BM cells expressing the oncogene BCR-ABL1 and Fubp1 shRNA (Fubp1 depletion) and mice that were transplanted with BM cells expressing BCR-ABL1 and scrambled shRNA (control) (18). BiSEK algorithm, PaDETO, detected one of the Fubp1 shRNA+ samples as an outlier (Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

“…For datasets used in this study, raw gene counts, were either created by us: (30), GEO accession number GSE122015, Figure 3 , or downloaded from the GEO: (A) Figure S2 , GEO accession number GSE140066 (B) Figure 4 , GEO accession number GSE124304 (18) (C) Figure 5-6 and Figures S3-S11 , GEO accession number GSE147507 (19). The results for all parts were created by following the GUI flow with BiSEK default parameters, unless specified.…”

Section: Methodsmentioning

confidence: 99%

“…We show that BiSEK was able to detect inconsistency in the data, resulting in improved strength of the test to detect affected genes. Analyzing data from FUBP1 depletion in Chronic Myeloid Leukemia (CML) cells of mice bone marrow that was generated by (18), we increased the power of the test and suggested a list of genes responsible for apoptosis, observed directly only experimentally in the study (18). We further tested the host response following SARS-CoV-2 infection, compared to that caused by other respiratory viruses (19).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

BiSEK: a platform for a reliable differential expression analysis

Haas

Light

Festinger

et al. 2021

Preprint

View full text Add to dashboard Cite

Differential Expression Analysis (DEA) of RNA-sequencing data is frequently performed for detecting key genes, affected across different conditions. Although DEA-workflows are well established, preceding reliability-testing of the input material, which is crucial for consistent and strong results, is challenging and less straightforward. Here we present Biological Sequence Expression Kit (BiSEK), a graphical user interface-based platform for DEA, dedicated to a reliable inquiry. BiSEK is based on a novel algorithm to track discrepancies between the data and the statistical model design. Moreover, BiSEK enables differential-expression analysis of groups of genes, to identify affected pathways, without relying on the significance of genes comprising them. Using BiSEK, we were able to improve previously conducted analysis, aimed to detect genes affected by FUBP1 depletion in chronic myeloid leukemia cells of mice bone-marrow. We found affected genes that are related to the regulation of apoptosis, supporting in-vivo experimental findings. We further tested the host response following SARS-CoV-2 infection. We identified a substantial interferon-I reaction and low expression levels of TLR3, an inducer of interferon-III (IFN-III) production, upon infection with SARS-CoV-2 compared to other respiratory viruses. This finding may explain the low IFN-III response upon SARS-CoV-2 infection. BiSEK is open-sourced, available as a web-interface.

show abstract

CRISPR/Cas‐mediated Fubp1 silencing disrupts circadian oscillation of Per1 protein via downregulating Syncrip expression

Kim

Sung

Shin

et al. 2019

Cell Biology International

View full text Add to dashboard Cite

Most living organisms have physiological and behavioral circadian rhythms controlled by molecular clocks. In mammals, several core clock genes show self‐perpetuating oscillation profiles of their messenger RNAs (mRNAs) and proteins through an auto‐regulatory transcription–translation feedback loop (TTFL). As a critical component in the molecular clock system, Period 1 (Per1) contributes to the maintenance of circadian rhythm duration predominantly in peripheral clocks. Alterations in Per1 expression and oscillating patterns lead to the development of cancers as well as circadian rhythm abnormalities. In this study, we demonstrate that the phasic profile of Per1 protein was clearly disrupted in CRISPR/Cas‐mediated Fubp1‐deficient cells. Although Fubp1 does not show rhythmic expression, Fubp1 upregulates the mRNA and protein level of Syncrip, the main post‐transcriptional regulator of Per1 protein oscillation. In addition to the diverse physiological functions of Fubp1, including cell‐cycle regulation and cellular metabolic control, our results suggest new roles for Fubp1 in the molecular clock system.

show abstract

The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia

Cited by 16 publications

References 37 publications

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

BiSEK: a platform for a reliable differential expression analysis

CRISPR/Cas‐mediated Fubp1 silencing disrupts circadian oscillation of Per1 protein via downregulating Syncrip expression

Contact Info

Product

Resources

About