The Role of TCOF1 Gene in Health and Disease: Beyond Treacher Collins Syndrome

Grzanka, Małgorzata; Piekiełko-Witkowska, Agnieszka

doi:10.3390/ijms22052482

Cited by 23 publications

(22 citation statements)

References 104 publications

(250 reference statements)

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“…Most of these isoforms contain exon 6A/treacle, a translational product of exon 6Acontained TCOF1 mRNA isoform [24], which is a nucleolar phosphoprotein with 1488 amino acids and a low-complexity three-domain structure [25]. TCOF1 and treacle are reported to regulate multiple key cellular processes, including ribosome biogenesis, mitosis, proliferation, cellular response to DNA damage, and apoptosis [26]. While TCOF1-related mechanisms in TCS have been extensively studied, research focused on the role of TCOF1 in malignancies is limited.…”

Section: Discussionmentioning

confidence: 99%

The oncogenic role of treacle ribosome biogenesis factor 1 (TCOF1) in human tumors: a pan-cancer analysis

Sun

Wang

et al. 2022

Aging

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Treacle ribosome biogenesis factor 1 (TCOF1) plays a crucial role in multiple processes, including ribosome biogenesis, DNA damage response (DDR), mitotic regulation, and telomere integrity. However, its role in cancers remains unclear. We aimed to visualize the expression, prognostic, and mutational landscapes of TCOF1 across cancers and to explore its association with immune infiltration. In this work, we integrated information from TCGA and GEO to explore the differential expression and prognostic value of TCOF1. Then, the mutational profiles of TCOF1 in cancers were investigated. We further determined the correlation between TCOF1 and immune cell infiltration levels. Additionally, we determined correlations among certain immune checkpoints, microsatellite instability, tumor mutational burden (TMB), and TCOF1. Potential pathways of TCOF1 in tumorigenesis were analyzed as well. In general, tumor tissue had a higher expression level of TCOF1 than normal tissue. The prognostic value of TCOF1 was multifaceted, depending on type of cancer. TCOF1 was correlated with tumor purity, CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells (DCs) in 6, 14, 16, 12, 20, 13, and 17 cancer types, respectively. TCOF1 might act on ATPase activity, microtubule binding, tubulin binding, and catalytic activity (on DNA), and participate in tumorigenesis through "cell cycle" and "cellular-senescence" pathways. TCOF1 could affect pan-cancer prognosis and was correlated with immune cell infiltration. "Cell cycle" and "cellular-senescence" pathways were involved in the functional mechanisms of TCOF1, a finding that awaits further experimental validation.

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Section: Discussionmentioning

confidence: 99%

The oncogenic role of treacle ribosome biogenesis factor 1 (TCOF1) in human tumors: a pan-cancer analysis

Sun

Wang

et al. 2022

Aging

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“…In the same theme of ubiquitination, genome stability, and DNA damage, TCOF1 (treacle ribosome biogenesis factor 1) has also been reported to function in ubiquitination through E3 ubiquitin ligase complex, RNA biogenesis, mitosis, proliferation, DNA damage response, and apoptosis [ 40 , 41 ]. There are reports that connect FUBP1 (far upstream element binding protein 1) and NUDT21 to the RNA binding, polyadenylation, and fine tuning of protein and RNA levels [ 41 , 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…There are reports that connect FUBP1 (far upstream element binding protein 1) and NUDT21 to the RNA binding, polyadenylation, and fine tuning of protein and RNA levels [ 41 , 42 ]. They both have been identified as potent pro-proliferative and anti-apoptotic factors by the modulation of complex networks in hematologic disorders and solid tumours [ 40 , 41 ]. Similarly, the BACH2–BCL6 interactors, EXOCS2 and SSB, also reported to interact with RNA and EXOCS2, are part of the highly conserved RNA processing/degrading exosome complex proteins in erythroid differentiation [ 43 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

Low BACH2 Expression Predicts Adverse Outcome in Chronic Lymphocytic Leukaemia

Ciardullo

Szołtysek

Zhou

et al. 2021

Cancers

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Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease with a highly variable clinical outcome. There are well-established CLL prognostic biomarkers that have transformed treatment and improved the understanding of CLL biology. Here, we have studied the clinical significance of two crucial B cell regulators, BACH2 (BTB and CNC homology 1, basic leucine zipper transcription factor 2) and BCL6 (B-cell CLL/lymphoma 6), in a cohort of 102 CLL patients and determined the protein interaction networks that they participate in using MEC-1 CLL cells. We observed that CLL patients expressing low levels of BCL6 and BACH2 RNA had significantly shorter overall survival (OS) than high BCL6- and BACH2-expressing cases. Notably, their low expression specifically decreased the OS of immunoglobulin heavy chain variable region-mutated (IGHV-M) CLL patients, as well as those with 11q and 13q deletions. Similar to the RNA data, a low BACH2 protein expression was associated with a significantly shorter OS than a high expression. There was no direct interaction observed between BACH2 and BCL6 in MEC-1 CLL cells, but they shared protein networks that included fifty different proteins. Interestingly, a prognostic index (PI) model that we generated, using integrative risk score values of BACH2 RNA expression, age, and 17p deletion status, predicted patient outcomes in our cohort. Taken together, these data have shown for the first time a possible prognostic role for BACH2 in CLL and have revealed protein interaction networks shared by BCL6 and BACH2, indicating a significant role for BACH2 and BCL6 in key cellular processes, including ubiquitination mediated B-cell receptor functions, nucleic acid metabolism, protein degradation, and homeostasis in CLL biology.

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“…A decrease in treacle could cause UBF rapid displacement from rDNA and then to the inhibition of rRNA synthesis. Increased expression of treacle may interfere with cisplatin-induced apoptosis [ 18 ]. Thus, both silencing and ectopic expression of TCOF1 coding treacle can cause apoptosis of neural crest cells during embryogenesis by influence on crucial apoptotic regulators [ 14 ].…”

Section: Geneticsmentioning

confidence: 99%

Treacher Collins Syndrome: Genetics, Clinical Features and Management

Marszałek-Kruk

Wójcicki

Dowgierd

et al. 2021

Genes

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Treacher Collins syndrome (TCS) is associated with abnormal differentiation of the first and second pharyngeal arches, occurring during fetal development. Features of TCS include microtia with conductive hearing loss, slanting palpebral fissures with possibly coloboma of the lateral part of lower eyelids, midface hypoplasia, micrognathia as well as sporadically cleft palate and choanal atresia or stenosis. TCS occurs in the general population at a frequency of 1 in 50,000 live births. Four subtypes of Treacher Collins syndrome exist. TCS can be caused by pathogenic variants in the TCOF1, POLR1D, POLR1C and POLR1B genes. Genetically, the TCOF1 gene contains 27 exons which encodes the Treacle protein. In TCOF1, over 200 pathogenic variants have been identified, of which most are deletions leading to a frame-shift, that result in the formation of a termination codon. In the presented article, we review the genetics and phenotype of TCS as well as the management and surgical procedures utilized for treatment.

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The Role of TCOF1 Gene in Health and Disease: Beyond Treacher Collins Syndrome

Cited by 23 publications

References 104 publications

The oncogenic role of treacle ribosome biogenesis factor 1 (TCOF1) in human tumors: a pan-cancer analysis

The oncogenic role of treacle ribosome biogenesis factor 1 (TCOF1) in human tumors: a pan-cancer analysis

Low BACH2 Expression Predicts Adverse Outcome in Chronic Lymphocytic Leukaemia

Treacher Collins Syndrome: Genetics, Clinical Features and Management

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