Transcriptional control of CBX5 by the RNA-binding proteins RBMX and RBMXL1 maintains chromatin state in myeloid leukemia

Prieto, Camila; Nguyen, Diu; Liu, Zhaoqi; Wheat, Justin C.; Perez, Almudena Chaves; Gourkanti, Saroj; Chou, Timothy; Barin, Ersilia; Velleca, Anthony; Rohwetter, Thomas; Chow, Arthur; Taggart, James; Savino, Angela Maria; Hoskova, Katerina; Dhodapkar, Meera; Schurer, Alexandra; Barlowe, Trevor; Vu, Ly; Leslie, Christina; Steidl, Ulrich; Rabadán, Raúl; Kharas, Michael G.

doi:10.1038/s43018-021-00220-w

Cited by 12 publications

(9 citation statements)

References 77 publications

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“…In our univariate analysis, low RBMX levels predict improved overall survival in patients with T-NHL (median OS 78.0 vs. 11.0 months; p < 0.001) and nodal T-NHL (median OS 124.0 vs. 13.0 months; p = 0.001) and also better progression-free survival in patients with T-NHL (median OS 17.0 vs. 7.0 months; p = 0.012). These results are consistent with a previous report which describes that RBMX controls myeloid leukemogenesis by regulating the chromatin state [ 21 ]. As a caveat, all patients with high RBMX expression died within 58 months after initial diagnosis.…”

Section: Discussionsupporting

confidence: 94%

“…In agreement with the previous reports, low RBMX expression levels predict better response to anthracycline-containing chemotherapy in patients with T-NHL (t-test p -value = 0.018; ROC-analysis AUC = 0.725). Former studies indicated an opposite association of RBMX expression levels and prognosis in different cancer types [ 7 , 17 , 18 , 20 , 21 ]. In our univariate analysis, low RBMX levels predict improved overall survival in patients with T-NHL (median OS 78.0 vs. 11.0 months; p < 0.001) and nodal T-NHL (median OS 124.0 vs. 13.0 months; p = 0.001) and also better progression-free survival in patients with T-NHL (median OS 17.0 vs. 7.0 months; p = 0.012).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, recent studies interestingly show poor outcome in hepatocellular carcinomas (HCC) [ 7 ] as well as head and neck cancers [ 20 ] when RBMX was highly expressed. Furthermore, RBMX was overexpressed in individuals with acute myeloid leukemia (AML) compared to healthy ones, and loss of RBMX delayed leukemia development [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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RBMX Protein Expression in T-Cell Lymphomas Predicts Chemotherapy Response and Prognosis

Schümann

Bauer

Groß

et al. 2021

Cancers

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T-cell non-Hodgkin’s lymphomas (T-NHL) are a heterogeneous group of lymphomas with a mature T-cell phenotype. While in some hematological diseases the prognosis improved over the last decades, T-NHL cases often relapse early or present with an initially refractory course. Recently, it has been shown that RNA binding proteins have a crucial role for malignant tumor initiation, progression and treatment response while contributing to chemotherapy resistance. Therefore, we investigated the protein expression of the RNA binding protein X (RBMX), which has been shown to be of great relevance in disease initiation and progression in hematological diseases in 53 T-NHL cases using conventional immunohistochemistry. Low RBMX expression was associated with better response to anthracycline-containing first-line treatment. Furthermore, low RBMX expression predicted an improved overall survival and progression-free survival in univariate analysis. Multivariable Cox regression revealed RBMX as an independent prognostic marker for overall survival (p = 0.007; hazard ratio (HR) = 0.204; 95% confidence interval (CI): 0.064–0.646) and progression-free survival (p = 0.006; HR = 0.235; 95% CI: 0.083–0.666). The study identifies low RBMX expression to predict better chemotherapy response, overall survival and progression-free survival in patients with T-cell non-Hodgkin’s lymphomas. These results suggest that RBMX protein expression levels might be a contributing factor towards chemotherapy resistance and thus affect prognosis. Hence, RBMX may be a potential therapeutic target and prognostic marker in T-cell lymphomas.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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RBMX Protein Expression in T-Cell Lymphomas Predicts Chemotherapy Response and Prognosis

Schümann

Bauer

Groß

et al. 2021

Cancers

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“…Missense mutations (P362L, A381T, and E384K) impacting the LCD of the RNA-binding protein T cell-restricted intracellular antigen-1 (TIA1) drive ALS and Frontotemporal Dementia (FTD) [ 82 ]. RBMX’s low-complexity region consists of a serine and arginine-rich region (SRR) followed by a tyrosine-rich region (TRR) is required for monitoring the expression of CBX5 mRNA encoding CBX5 protein in the hematological malignancy acute myeloid leukemia (AML) cells [ 83 ] …”

Section: Rbps Assume Diverse Types Of Functions In Mammalian Cellsmentioning

confidence: 99%

Roles of RNA-binding proteins in neurological disorders, COVID-19, and cancer

2022

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RNA-binding proteins (RBPs) have emerged as important players in multiple biological processes including transcription regulation, splicing, R-loop homeostasis, DNA rearrangement, miRNA function, biogenesis, and ribosome biogenesis. A large number of RBPs had already been identified by different approaches in various organisms and exhibited regulatory functions on RNAs’ fate. RBPs can either directly or indirectly interact with their target RNAs or mRNAs to assume a key biological function whose outcome may trigger disease or normal biological events. They also exert distinct functions related to their canonical and non-canonical forms. This review summarizes the current understanding of a wide range of RBPs’ functions and highlights their emerging roles in the regulation of diverse pathways, different physiological processes, and their molecular links with diseases. Various types of diseases, encompassing colorectal carcinoma, non-small cell lung carcinoma, amyotrophic lateral sclerosis, and Severe acute respiratory syndrome coronavirus 2, aberrantly express RBPs. We also highlight some recent advances in the field that could prompt the development of RBPs-based therapeutic interventions.

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“…The differential GO-BP of "regulation of alternative mRNA splicing, via spliceosome" in the liver of Trpv1 KO mice indicated enhanced RNA processing, which is in line with the downregulation of H2BC9, H2BC4, and H1-0 (core components of nucleosomes, Figure 3B). Proteins clustered in this enriched GO-BP may regulate a variety of post-transcriptional processes (e.g., alternative splicing, nucleocytoplasmic transport, translation, and degradation) under stress conditions and cellular reprogramming [51,52]. Of these, THRAP3 promotes the binding of CLOCK-BMAL1 to DNA and links it to the basic transcriptional machinery [53]; it is also required for the DNA damage response, control of mRNA splicing, and nuclear mRNA degradation [54].…”

Section: Lack Of Trpv1 Channel Affects Proteome and Disrupts Biologic...mentioning

confidence: 99%

Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes

Lacerda

Gomes

Zanetti

et al. 2022

IJMS

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To investigate the role of the transient receptor potential channel vanilloid type 1 (TRPV1) in hepatic glucose metabolism, we analyzed genes related to the clock system and glucose/lipid metabolism and performed glycogen measurements at ZT8 and ZT20 in the liver of C57Bl/6J (WT) and Trpv1 KO mice. To identify molecular clues associated with metabolic changes, we performed proteomics analysis at ZT8. Liver from Trpv1 KO mice exhibited reduced Per1 expression and increased Pparα, Pparγ, Glut2, G6pc1 (G6pase), Pck1 (Pepck), Akt, and Gsk3b expression at ZT8. Liver from Trpv1 KO mice also showed reduced glycogen storage at ZT8 but not at ZT20 and significant proteomics changes consistent with enhanced glycogenolysis, as well as increased gluconeogenesis and inflammatory features. The network propagation approach evidenced that the TRPV1 channel is an intrinsic component of the glucagon signaling pathway, and its loss seems to be associated with increased gluconeogenesis through PKA signaling. In this sense, the differentially identified kinases and phosphatases in WT and Trpv1 KO liver proteomes show that the PP2A phosphatase complex and PKA may be major players in glycogenolysis in Trpv1 KO mice.

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Transcriptional control of CBX5 by the RNA-binding proteins RBMX and RBMXL1 maintains chromatin state in myeloid leukemia

Cited by 12 publications

References 77 publications

RBMX Protein Expression in T-Cell Lymphomas Predicts Chemotherapy Response and Prognosis

RBMX Protein Expression in T-Cell Lymphomas Predicts Chemotherapy Response and Prognosis

Roles of RNA-binding proteins in neurological disorders, COVID-19, and cancer

Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes

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