PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity

Geng, Guangfeng; Xu, Changlu; Peng, Nan; Li, Yue; Liu, Jinhua; Wu, Jing; Liang, Jing; Zhu, Yushan; Shi, Lihong

doi:10.1111/imm.13304

Cited by 15 publications

(13 citation statements)

References 62 publications

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“…Of those genes, 19% (536/2,874 for HUR) and 22% (636/2,855 of PTBP1) were significantly stronger bound when both RBPs acted together (Figure S4E). In comparison to all 6,885 HUR-and PTBP1-bound genes, the uniquely and differentially bound genes in the co-RAPseq assay were functionally enriched in innate immune response pathways (Figure S4F) as previously observed for each factor individually (Christodoulou-Vafeiadou et al, 2018;Geng et al, 2021;Rothamel et al, 2021;Sasanuma et al, 2019;Sueyoshi et al, 2018). Remarkably, the strongest cooperative sites resided within introns of these pathways signifying cooperative functions of HUR and PTBP1 in mRNA pre-processing (Figure S4G).…”

Section: Hur and Ptbp1 Cooperate Post-transcriptionally By Keeping A Specific Distance Between Binding Sitessupporting

confidence: 68%

Large-scale identification of RBP-RNA interactions by RAPseq refines essentials of post-transcriptional gene regulation

Atanasoai

Papavasileiou

Preiß

et al. 2021

Preprint

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SUMMARYOver the past decade, thousands of putative human RNA binding proteins (RBPs) have been identified and increased the demand for specifying RNA binding capacities. Here, we developed RNA affinity purification followed by sequencing (RAPseq) that enables in vitro large-scale profiling of RBP binding to native RNAs. First, by employing RAPseq, we found that vertebrate HURs recognize a conserved RNA binding motif and bind predominantly to introns in zebrafish compared to 3’UTRs in human RNAs. Second, our dual RBP assays (co-RAPseq) uncovered cooperative RNA binding of HUR and PTBP1 within an optimal distance of 27 nucleotides. Third, we developed T7-RAPseq to discern m6A-dependent and - independent RNA binding sites of YTHDF1. Fourth, RAPseq of 26 novel non-canonical RBPs revealed specialized moonlighting interactions. Last, five pathological IGF2BP family variants exhibited different RNA binding patterns. Overall, our simple, scalable and versatile method enables to fast-forward RBP-related questions.Graphical AbstractHIGHLIGHTSRAPseq reveals in vitro-derived RBP-RNA interactomesthe vertebrate-conserved HUR binding motif adapted to species-unique RNA featuresco-RAPseq and T7-RAPseq uncover binding cooperativity and modification dependenciesnon-canonical RBPs have specialized RNA interactomes

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Section: Hur and Ptbp1 Cooperate Post-transcriptionally By Keeping A Specific Distance Between Binding Sitessupporting

confidence: 68%

Large-scale identification of RBP-RNA interactions by RAPseq refines essentials of post-transcriptional gene regulation

Atanasoai

Papavasileiou

Preiß

et al. 2021

Preprint

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“…PTBP1 has been found to be correlated with tumor metastasis, which leads to a poor prognosis in patients [ 12 ]. It mediates tumor development by regulating the cellular metabolism [ 13 ] and immune response of T/B lymphocytes as a splicing regulator [ 14 , 15 ], which has an effect on the immune infiltration of tumor cells. PTBP1 plays a wide range of roles in tumorigenesis, so it may be proven as a novel therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

PTBP1 as a Promising Predictor of Poor Prognosis by Regulating Cell Proliferation, Immunosuppression, and Drug Sensitivity in SARC

Gong

Jiang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Sarcomas (SARC) have been found as rare and heterogeneous malignancies with poor prognosis. PTBP1, belonging to the hnRNPs family, plays an essential role in some biological functions (e.g., pre-mRNA splicing, cell growth, and nervous system development). However, the role of PTBP1 in SARC remains unclear. In this study, the aim was to investigate the potential role of PTBP1 with a focus on SARC. Methods. The expression, prognostic value, possible biological pathways of PTBP1, and its relationship with immune infiltration and drug sensitivity were comprehensively analyzed based on multiple databases. PTBP1 was further validated in osteosarcoma as the most prominent bone SARC. The expression of PTBP1 was investigated through IHC. The prognostic value of PTBP1 was verified in TARGET-OS databases. CRISPR/Cas9-mediated PTBP1 knockout HOS human osteosarcoma cell lines were used to assess the effect of PTBP1 on cell proliferation, migration, metastasis and cell cycle by CCK-8, Transwell migration, invasion, and FACS experiment. Result. PTBP1 was highly expressed and significantly correlated with poor prognosis in several cancers, especially in SARC, which was validated in the clinical cohort and osteosarcoma cell lines. The genetic alteration of PTBP1 was found most frequently in SARC. Besides, PTBP1 played a role in oncogenesis and immunity through cell cycle, TGFB, autophagy, and WNT pathways at a pan-cancer level. Knockout of PTBP1 was observed to negatively affect proliferation, migration, metastasis, and cell cycle of osteosarcoma in vitro. Furthermore, PTBP1 was significantly correlated with tumor immune infiltration, DNA methylation, TMB, and MSI in a wide variety of cancers. Moreover, the potential of the expression level of PTBP1 in predicting drug sensitivity was assessed. Conclusions. PTBP1 is highly expressed and correlated with prognosis and plays a vital pathogenic role in oncogenesis and immune infiltration of various cancers, especially for SARC, which suggests that it may be a promising prognostic marker and therapeutic target in the future.

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“…PTBP1 is an RNA-binding protein involved in splicing. In dendritic cells, it was found that PTBP1 regulates the expression of several IFN-regulated genes [ 43 ]. PTBP1 is expressed by melanoma stem cells [ 44 ] and it has been shown to regulate CD44v6 expression in melanoma brain metastases [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Tumor Cell Associated Type I IFN Resistance Gene Expression Signature of Human Melanoma, the Components of Which Have a Predictive Potential for Immunotherapy

Ladányi

Rásó

Barbai

et al. 2022

IJMS

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We developed a human melanoma model using the HT168-M1 cell line to induce IFN-α2 resistance in vitro (HT168-M1res), which was proven to be maintained in vivo in SCID mice. Comparing the mRNA profile of in vitro cultured HT168-M1res cells to its sensitive counterpart, we found 79 differentially expressed genes (DEGs). We found that only a 13-gene core of the DEGs was stable in vitro and only a 4-gene core was stable in vivo. Using an in silico cohort of IFN-treated melanoma tissues, we validated a differentially expressed 9-gene core of the DEGs. Furthermore, using an in silico cohort of immune checkpoint inhibitor (ICI)-treated melanoma tissues, we tested the predictive power of the DEGs for the response rate. Analysis of the top four upregulated and top four downregulated genes of the DEGs identified WFDC1, EFNA3, DDX10, and PTBP1 as predictive genes, and analysis of the “stable” genes of DEGs for predictive potential of ICI response revealed another 13 genes, out of which CDCA4, SOX4, DEK, and HSPA1B were identified as IFN-regulated genes. Interestingly, the IFN treatment associated genes and the ICI-therapy predictive genes overlapped by three genes: WFDC1, BCAN, and MT2A, suggesting a connection between the two biological processes.

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PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity

Cited by 15 publications

References 62 publications

Large-scale identification of RBP-RNA interactions by RAPseq refines essentials of post-transcriptional gene regulation

Large-scale identification of RBP-RNA interactions by RAPseq refines essentials of post-transcriptional gene regulation

PTBP1 as a Promising Predictor of Poor Prognosis by Regulating Cell Proliferation, Immunosuppression, and Drug Sensitivity in SARC

Identification of a Tumor Cell Associated Type I IFN Resistance Gene Expression Signature of Human Melanoma, the Components of Which Have a Predictive Potential for Immunotherapy

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