PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer

Chen, Chen; Shang, Anquan; Gao, Yuting; Huang, Jingjuan; Liu, Gege; Cho, William C.; Liu, Dong

doi:10.3389/fmolb.2022.968458

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…Ptbp3 encodes a protein that is critical in RNA splicing and transcriptional regulation ( Xie et al, 2022 ). The PTBP3 protein mediates TGF-β-induced epithelial-to-mesenchymal transition ( Dong et al, 2022 ) and can serve as an immunomodulatory biomarker of cancer ( Chen et al, 2022 ). Its expression and function in mast cells is unknown.…”

Section: Discussionmentioning

confidence: 99%

Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators

Kulka

Wagner

Cho

et al. 2023

Front. Bioeng. Biotechnol.

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Introduction: Mast cells are highly granulated tissue-resident leukocytes that require a three-dimensional matrix to differentiate and mediate immune responses. However, almost all cultured mast cells rely on two-dimensional suspension or adherent cell culture systems, which do not adequately reflect the complex structure that these cells require for optimal function.Methods: Crystalline nanocellulose (CNC), consisting of rod-like crystals 4–15 nm in diameter and 0.2–1 µm in length, were dispersed in an agarose matrix (12.5% w/v), and bone marrow derived mouse mast cells (BMMC) were cultured on the agarose/CNC composite. BMMC were activated with the calcium ionophore A23187 or immunoglobulin E (IgE) and antigen (Ag) to crosslink high affinity IgE receptors (FcεRI).Results: BMMC cultured on a CNC/agarose matrix remained viable and metabolically active as measured by reduction of sodium 3′-[1-[(phenylamino)-carbony]-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT), and the cells maintained their membrane integrity as analyzed by measuring the release of lactate dehydrogenase (LDH) and propidium iodide exclusion by flow cytometry. Culture on CNC/agarose matrix had no effect on BMMC degranulation in response to IgE/Ag or A23187. However, culture of BMMC on a CNC/agarose matrix inhibited A23187-and IgE/Ag-activated production of tumor necrosis factor (TNF) and other mediators such as IL-1β, IL-4, IL-6, IL-13, MCP-1/CCL2, MMP-9 and RANTES by as much as 95%. RNAseq analysis indicated that BMMC expressed a unique and balanced transcriptome when cultured on CNC/agarose.Discussion: These data demonstrate that culture of BMMCs on a CNC/agarose matrix promotes cell integrity, maintains expression of surface biomarkers such as FcεRI and KIT and preserves the ability of BMMC to release pre-stored mediators in response to IgE/Ag and A23187. However, culture of BMMC on CNC/agarose matrix inhibits BMMC production of de novo synthesized mediators, suggesting that CNC may be altering specific phenotypic characteristics of these cells that are associated with late phase inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators

Kulka

Wagner

Cho

et al. 2023

Front. Bioeng. Biotechnol.

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“…PTBP-modulated control of AS is frequently disturbed in cancer and deregulated expression of PTBPs is associated with adverse disease outcome in various malignancies (10)(11)(12). Elevated expression of PTBP1, the most abundant PTBP paralogue in most cancers, is associated with poor outcome in various solid cancers and associated with clinical properties suggesting roles of PTBPs in cancer progression (12). In agreement, PTBPs have been reported to influence key signaling pathways, e.g.…”

Section: Introductionmentioning

confidence: 89%

“…Positional rules guiding this PTBP-dependent modulation of splicing were recently demonstrated by a capture RIC-seq (CRIC-seq) method, which enriches RBPassociated RNA-RNA fragments (9). PTBP-modulated control of AS is frequently disturbed in cancer and deregulated expression of PTBPs is associated with adverse disease outcome in various malignancies (10)(11)(12). Elevated expression of PTBP1, the most abundant PTBP paralogue in most cancers, is associated with poor outcome in various solid cancers and associated with clinical properties suggesting roles of PTBPs in cancer progression (12).…”

Section: Introductionmentioning

confidence: 99%

RAVER1 interconnects lethal EMT and miR/RISC activity by the control of alternative splicing

Wedler

Bley

Glaß

et al. 2023

Preprint

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The RAVER1 protein was proposed to serve as a co-factor in guiding the PTBP-dependent control of alternative splicing (AS). Whether RAVER1 solely acts in concert with PTBPs and how it affects cancer cell fate remained elusive. Here we provide the first comprehensive investigation of RAVER1-controlled AS in cancer cell models and reveal a pro-oncogenic role of RAVER1 in tumor growth. This unravels that RAVER1 guides AS in synergy with PTBPs but more prominently serves PTBP1-independent roles in splicing. In cancer cells, one major function of RAVER1 is the control of proliferation and apoptosis, which involves the modulation of AS events within the miR/RISC pathway. Associated with this regulatory role, RAVER1 antagonizes lethal, TGFB-driven epithelial-mesenchymal-transition (EMT) by limiting TGFB signaling. RAVER1-modulated splicing events affect the insertion of protein interaction modules in factors guiding miR/RISC-dependent gene silencing. Most prominently, in all three human TNRC6 proteins, RAVER1 controls AS of GW-enriched motifs, which are essential for AGO2-binding. Disturbance of RAVER1-guided AS events in TNRC6 proteins and other facilitators of miR/RISC activity compromise miR/RISC activity which is essential to restrict TGFB signaling and lethal EMT.

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“…PTBP-modulated control of AS is frequently disturbed in cancer and deregulated expression of PTBPs is associated with adverse disease outcome in various malignancies ( 10–12 ). Elevated expression of PTBP1, the most abundant PTBP paralogue in most cancers, is associated with poor outcome in various solid cancers and clinical properties suggesting roles of PTBPs in cancer progression ( 12 ). In agreement, PTBPs have been reported to influence key signaling pathways, e.g.…”

Section: Introductionmentioning

confidence: 99%

RAVER1 hinders lethal EMT and modulates miR/RISC activity by the control of alternative splicing

Wedler,

Bley,

Glaß

et al. 2024

Nucleic Acids Research

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The RAVER1 protein serves as a co-factor in guiding the polypyrimidine tract-binding protein (PTBP)-dependent control of alternative splicing (AS). Whether RAVER1 solely acts in concert with PTBPs and how it affects cancer cell fate remained elusive. Here, we provide the first comprehensive investigation of RAVER1-controlled AS in cancer cell models. This reveals a pro-oncogenic role of RAVER1 in modulating tumor growth and epithelial-mesenchymal-transition (EMT). Splicing analyses and protein-association studies indicate that RAVER1 guides AS in association with other splicing regulators, including PTBPs and SRSFs. In cancer cells, one major function of RAVER1 is the stimulation of proliferation and restriction of apoptosis. This involves the modulation of AS events within the miR/RISC pathway. Disturbance of RAVER1 impairs miR/RISC activity resulting in severely deregulated gene expression, which promotes lethal TGFB-driven EMT. Among others, RAVER1-modulated splicing events affect the insertion of protein interaction modules in factors guiding miR/RISC-dependent gene silencing. Most prominently, in all three human TNRC6 proteins, RAVER1 controls AS of GW-enriched motifs, which are essential for AGO2-binding and the formation of active miR/RISC complexes. We propose, that RAVER1 is a key modulator of AS events in the miR/RISC pathway ensuring proper abundance and composition of miR/RISC effectors. This ensures balanced expression of TGFB signaling effectors and limits TGFB induced lethal EMT.

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PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer

Cited by 6 publications

References 45 publications

Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators

Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators

RAVER1 interconnects lethal EMT and miR/RISC activity by the control of alternative splicing

RAVER1 hinders lethal EMT and modulates miR/RISC activity by the control of alternative splicing

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