Pan-Cancer Analysis Reveals the Relation between TRMT112 and Tumor Microenvironment

Xu, Haitao; Jiang, Caihong; Yao, Fusheng; Liang, Hong; Yan, Hong; Chen, Dangui; Wu, Youzhi; Zhong, Linhao

doi:10.1155/2022/1445932

Cited by 6 publications

(3 citation statements)

References 49 publications

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“…Bud23 is methylated by Trm112 in S. cerevisiae , while Trmt112, the methyltransferase homolog, carries out this reaction in humans. TRM112 and TRMT112 are AdoMet-dependent methyltransferases, which play a role in ribosome biogenesis and cell proliferation in both humans and S. cerevisiae , and have also been identified as being involved in tumor formation in humans ( Xu et al . 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Profiling the compendium of changes in Saccharomyces cerevisiae due to mutations that alter availability of the main methyl donor S-Adenosylmethionine

Remines,

Schoonover,

Knox

et al. 2024

G3: Genes, Genomes, Genetics

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The SAM1 and SAM2 genes encode for S-AdenosylMethionine (AdoMet) synthetase enzymes, with AdoMet serving as the main cellular methyl donor. We have previously shown that independent deletion of these genes alters chromosome stability and AdoMet concentrations in opposite ways in Saccharomyces cerevisiae. To characterize other changes occurring in these mutants, we grew wildtype, sam1Δ/sam1Δ, and sam2Δ/sam2Δ strains in 15 different Phenotypic Microarray plates with different components and measured growth variations. RNA-Sequencing was also carried out on these strains and differential gene expression determined for each mutant. We explored how the phenotypic growth differences are linked to the altered gene expression, and hypothesize mechanisms by which loss of the SAM genes and subsequent AdoMet level changes, impact pathways and processes. We present six stories, discussing changes in sensitivity or resistance to azoles, cisplatin, oxidative stress, arginine biosynthesis perturbations, DNA synthesis inhibitors, and tamoxifen, to demonstrate the power of this novel methodology to broadly profile changes due to gene mutations. The large number of conditions that result in altered growth, as well as the large number of differentially expressed genes with wide-ranging functionality, speaks to the broad array of impacts that altering methyl donor abundance can impart. Our findings demonstrate that some cellular changes are directly related to AdoMet-dependent methyltransferases and AdoMet availability, some are directly linked to the methyl cycle and its role in production of several important cellular components, and others reveal impacts of SAM gene mutations on previously unconnected pathways.

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Section: Discussionmentioning

confidence: 99%

Profiling the compendium of changes in Saccharomyces cerevisiae due to mutations that alter availability of the main methyl donor S-Adenosylmethionine

Remines,

Schoonover,

Knox

et al. 2024

G3: Genes, Genomes, Genetics

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show abstract

“… 42 TRMT112 not only participated in multiple biological processes, including cell proliferation and DNA damage, 43 but also exhibited positive correlation with various immune cells, such as dendritic cells, T cells and macrophages. 44 In summary, GMPI is likely to be a prognostic indicator to evaluate the aggressiveness and immune status of OC.…”

Section: Discussionmentioning

confidence: 99%

Glutamine metabolism prognostic index predicts tumour microenvironment characteristics and therapeutic efficacy in ovarian cancer

Gao,

Wei,

Ying

et al. 2024

J Cellular Molecular Medi

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Mounting evidence has highlighted the multifunctional characteristics of glutamine metabolism (GM) in cancer initiation, progression and therapeutic regimens. However, the overall role of GM in the tumour microenvironment (TME), clinical stratification and therapeutic efficacy in patients with ovarian cancer (OC) has not been fully elucidated. Here, three distinct GM clusters were identified and exhibited different prognostic values, biological functions and immune infiltration in TME. Subsequently, glutamine metabolism prognostic index (GMPI) was constructed as a new scoring model to quantify the GM subtypes and was verified as an independent predictor of OC. Patients with low‐GMPI exhibited favourable survival outcomes, lower enrichment of several oncogenic pathways, less immunosuppressive cell infiltration and better immunotherapy responses. Single‐cell sequencing analysis revealed a unique evolutionary trajectory of OC cells from high‐GMPI to low‐GMPI, and OC cells with different GMPI might communicate with distinct cell populations through ligand‐receptor interactions. Critically, the therapeutic efficacy of several drug candidates was validated based on patient‐derived organoids (PDOs). The proposed GMPI could serve as a reliable signature for predicting patient prognosis and contribute to optimising therapeutic strategies for OC.

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“…In pancreatic cancer, TRMT112 and WBSCR22 synergistically inhibit pancreatic cancer progression by repressing ISG15 transcription, which seems to support the possibility that TRMT112 is a tumor suppressor [ 106 ]. However, another report showed that TRMT112 was significantly upregulated in multiple cancers and was accompanied by a poorer prognosis [ 107 ]. Therefore, further validation is required to ascertain the involvement of TRMT112 and TRMT11/THUMPD2/THUMPD3 in the proliferation of diverse cancer cells.…”

Section: Trna Biological Functionmentioning

confidence: 99%

Dysregulation of tRNA methylation in cancer: Mechanisms and targeting therapeutic strategies

Yuan,

Zhang,

Lyu

et al. 2024

Cell Death Discov.

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AbstracttRNA is the RNA type that undergoes the most modifications among known RNA, and in recent years, tRNA methylation has emerged as a crucial process in regulating gene translation. Dysregulation of tRNA abundance occurs in cancer cells, along with increased expression and activity of tRNA methyltransferases to raise the level of tRNA modification and stability. This leads to hijacking of translation and synthesis of multiple proteins associated with tumor proliferation, metastasis, invasion, autophagy, chemotherapy resistance, and metabolic reprogramming. In this review, we provide an overview of current research on tRNA methylation in cancer to clarify its involvement in human malignancies and establish a theoretical framework for future therapeutic interventions targeting tRNA methylation processes.

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Pan-Cancer Analysis Reveals the Relation between TRMT112 and Tumor Microenvironment

Cited by 6 publications

References 49 publications

Profiling the compendium of changes in Saccharomyces cerevisiae due to mutations that alter availability of the main methyl donor S-Adenosylmethionine

Profiling the compendium of changes in Saccharomyces cerevisiae due to mutations that alter availability of the main methyl donor S-Adenosylmethionine

Glutamine metabolism prognostic index predicts tumour microenvironment characteristics and therapeutic efficacy in ovarian cancer

Dysregulation of tRNA methylation in cancer: Mechanisms and targeting therapeutic strategies

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