Systematic analysis of glutamine metabolism family genes and exploration of the biological role of GPT in colorectal cancer

Dai, Weiqi; Mo, Wenhui; Xu, Wenqiang; Han, Dengyu; Xu, Xuanfu

doi:10.18632/aging.205079

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…Some amino acids specifically “glutamine” appear to play a prominent role in immunomodulation, proliferation, and activation of T cells and also malignant tumor progression, especially in their myeloid group [ 23 – 25 ]. Glutamine, the most abundant amino acid in the human body, is the second most important nutrient for cell proliferation, after glucose [ 25 , 26 ]. Glutamine metabolism is very closely connected to mTORC1, a master controller of cell growth and metabolism [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

TIM-3/Galectin-9 interaction and glutamine metabolism in AML cell lines, HL-60 and THP-1

Shapourian,

Ghanadian,

Eskandari

et al. 2024

BMC Cancer

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Background T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a cell surface molecule that was first discovered on T cells. However, recent studies revealed that it is also highly expressed in acute myeloid leukemia (AML) cells and it is related to AML progression. As, Glutamine appears to play a prominent role in malignant tumor progression, especially in their myeloid group, therefore, in this study we aimed to evaluate the relation between TIM-3/Galectin-9 axis and glutamine metabolism in two types of AML cell lines, HL-60 and THP-1. Methods Cell lines were cultured in RPMI 1640 which supplemented with 10% FBS and 1% antibiotics. 24, 48, and 72 h after addition of recombinant Galectin-9 (Gal-9), RT-qPCR analysis, RP-HPLC and gas chromatography techniques were performed to evaluate the expression of glutaminase (GLS), glutamate dehydrogenase (GDH) enzymes, concentration of metabolites; Glutamate (Glu) and alpha-ketoglutarate (α-KG) in glutaminolysis pathway, respectively. Western blotting and MTT assay were used to detect expression of mammalian target of rapamycin complex (mTORC) as signaling factor, GLS protein and cell proliferation rate, respectively. Results The most mRNA expression of GLS and GDH in HL-60 cells was seen at 72 h after Gal-9 treatment (p = 0.001, p = 0.0001) and in THP-1 cell line was observed at 24 h after Gal-9 addition (p = 0.001, p = 0.0001). The most mTORC and GLS protein expression in HL-60 and THP-1 cells was observed at 72 and 24 h after Gal-9 treatment (p = 0.0001), respectively. MTT assay revealed that Gal-9 could promote cell proliferation rate in both cell lines (p = 0.001). Glu concentration in HL-60 and α-KG concentration in both HL-60 (p = 0.03) and THP-1 (p = 0.0001) cell lines had a decreasing trend. But, Glu concentration had an increasing trend in THP-1 cell line (p = 0.0001). Conclusion Taken together, this study suggests TIM-3/Gal-9 interaction could promote glutamine metabolism in HL-60 and THP-1 cells and resulting in AML development.

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Section: Introductionmentioning

confidence: 99%

TIM-3/Galectin-9 interaction and glutamine metabolism in AML cell lines, HL-60 and THP-1

Shapourian,

Ghanadian,

Eskandari

et al. 2024

BMC Cancer

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Glutamic-pyruvic transaminase 1 deficiency–mediated metabolic reprogramming facilitates colorectal adenoma-carcinoma progression

Xiong,

Yang,

Liu

et al. 2025

Sci. Transl. Med.

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The tumorigenesis of colorectal cancer (CRC) often follows the normal-adenoma-carcinoma (N-A-C) sequence. However, the molecular mechanisms underlying colorectal adenoma carcinogenesis remain largely unknown. Here, we analyzed transcriptomic profile changes in normal, advanced adenoma, and carcinoma tissues from patients with CRC, revealing that glutamic-pyruvic transaminase 1 ( GPT1 ) in colorectal tissues was down-regulated during the N-A-C process and correlated with poor CRC prognosis. Mechanistically, GPT1 was transcriptionally activated by Krüppel-like factor 4 (KLF4). GPT1 reprogrammed metabolism and suppressed CRC tumorigenesis in cells and mouse models not only through enzyme-dependent α-ketoglutarate (α-KG) production and WNT signaling inhibition but also through enzyme-independent disruption of the folate cycle through binding with methylenetetrahydrofolate dehydrogenase 1–like (MTHFD1L). Furthermore, we identified poliumoside as a GPT1 activator that restrained CRC progression in cells, patient-derived CRC organoids, and patient-derived xenograft (PDX) models of CRC. Our study uncovers a role for GPT1 in CRC tumorigenesis and shows that poliumoside is a potential drug for the prevention and treatment of CRC.

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Evaluation of Large Language Models in Tailoring Educational Content for Disadvantaged Cancer Survivors and Their Caregivers (Preprint)

Liu,

Hu,

Xiao

et al. 2024

Preprint

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BACKGROUND Disadvantaged cancer survivors and their caregivers (e.g., individuals with limited health literacy, racial and ethnic minorities facing language barriers) face a disproportionately increased risk of symptom burden from cancer and its treatments. Large language models (LLMs) offer researchers an opportunity to develop educational materials tailored to these populations. OBJECTIVE The purposes of this study were to: 1) evaluate the overall performance of LLMs in generating tailored educational content for disadvantaged cancer survivors and their caregivers; 2) compare the performances of three Generative Pre-trained Transformer (GPT) models (i.e., GPT-3.5 Turbo, GPT-4, GPT-4 Turbo); and 3) explore different prompts that can help LLMs generate better content. METHODS We selected 30 topics from national guidelines on cancer care and education. GPT-3.5 Turbo, GPT-4, and GPT-4 Turbo were used to generate tailored content of up to 250 words at a 6th-grade reading level, with translations into Spanish and Chinese for each topic. Nine oncology experts evaluated the content based on pre-determined criteria: word limit, reading level, and quality assessment (i.e., clarity, accuracy, relevance, completeness, and comprehensibility). ANOVA or Chi-square analyses were employed to compare differences among the various GPT models and prompts. RESULTS Overall, LLMs showed excellent performance in tailoring educational content, with 74.2% (n=360) adhering to the specified word limit and achieving an average quality assessment score of 8.933 out of 10. However, LLMs showed moderate performance in reading level, with 41.1% of content failing to meet the 6th-grade reading level. LLMs demonstrated strong translation capabilities, achieving an accuracy of 88.9% for Spanish and 81.1% for Chinese translations. The more advanced GPT-4 family models showed better overall performance compared to GPT-3.5 Turbo. Prompting GPTs to produce bulleted-format content was likely to result in better educational materials compared to textual-format content. CONCLUSIONS This study highlights the application of LLMs in cancer care and education while acknowledging their potential limitations. The findings can inform the development and implementation of interventions in cancer symptom management and supportive care, thereby advancing health equity. INTERNATIONAL REGISTERED REPORT RR2-10.2196/48499

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Systematic analysis of glutamine metabolism family genes and exploration of the biological role of GPT in colorectal cancer

Cited by 3 publications

References 48 publications

TIM-3/Galectin-9 interaction and glutamine metabolism in AML cell lines, HL-60 and THP-1

TIM-3/Galectin-9 interaction and glutamine metabolism in AML cell lines, HL-60 and THP-1

Glutamic-pyruvic transaminase 1 deficiency–mediated metabolic reprogramming facilitates colorectal adenoma-carcinoma progression

Evaluation of Large Language Models in Tailoring Educational Content for Disadvantaged Cancer Survivors and Their Caregivers (Preprint)

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