A Targeted Bioinformatics Assessment of Adrenocortical Carcinoma Reveals Prognostic Implications of GABA System Gene Expression

Knott, Erika L.; Leidenheimer, Nancy J.

doi:10.3390/ijms21228485

Cited by 14 publications

(9 citation statements)

References 146 publications

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“…GABAT, encoded by the ABAT gene, is mainly implicated in the GABA transamination process and was found to play an important role in the GABA shunt pathway [ 21 ]. The present work investigated the relationship between enzyme activity of GABAT and HMAs sensitivity.…”

Section: Discussionmentioning

confidence: 99%

ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling

Zhao

Wang

et al. 2022

Cell Death Discov.

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The factors that affect hypomethylating agents (HMAs) sensitivity in myelodysplastic syndrome (MDS) are complex and multifaceted. They include DNA methylation, gene expression, mutation, etc. However, the underlying mechanisms are still not clearly illustrated. In the present work, ABAT gene expression was associated with HMAs sensitivity. It was found that ABAT gene interference increased the sensitivity of HL-60 and THP-1 cells to HMAs treatment, while ABAT overexpression decreased its sensitivity. RNA-sequencing analysis showed that ABAT knockdown activated both interferon I and interferon-gamma signaling while inhibiting the secondary metabolic synthesis and arginine metabolic process. Gas chromatography-mass spectrometry (GC-MS) based metabolic profiling also demonstrated that ABAT gene knockdown affected arginine, alanine, aspartate, and glutamate metabolism, in addition to the biosynthesis of valine, leucine, and isoleucine, and the metabolism of beta-alanine. The ABAT gene expression downregulation could activate the CXCR4/mTOR signaling pathway, which was related to HMAs sensitivity. CXCR4 expression was regulated by mTOR activity and vice versa. In vivo, mice injected with ABAT gene knockdown cells lived longer than control mice after HMAs treatment. Overall, this study elucidates the novel regulatory mechanisms of HMAs sensitivity and provides a potential therapeutic target in MDS.

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Section: Discussionmentioning

confidence: 99%

ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling

Zhao

Wang

et al. 2022

Cell Death Discov.

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“…Driver gene alterations show a higher level of heterogeneity while methylation and chromosomal alterations profiles are more stable and they may serve as prognostic markers. 2020/ Knott [63] Analysis of (TCGA) the expression of 30 genes encoding the g-aminobutyric acid (GABA) system in TGCA ACC dataset.…”

Section: / Zhu [59]mentioning

confidence: 99%

“…In the predefined time frame, 29 original works were published and a summary is provided in Table 2[50,51 ▪ ,52 ▪ ,54–67,68 ▪ ,69–75].…”

Section: Systematic Analysis Of Literature 2019–2021 Of Molecular Gen...mentioning

confidence: 99%

“…Furthermore, analysis of methylation of single G0/S2 gene is affordable and it could become an useful marker of hypermethylation in clinical practice [ 52 ▪ ]. Another study dealing with prognostic impact of methylation has been published by Creemers et al [ 63 ]. In this ENSAT study, the methylation status of IGF2 promoter regions was validated along with other clinico-pathological factors.…”

Section: Systematic Analysis Of Literature 2019–2021 Of Molecular Gen...mentioning

confidence: 99%

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Molecular genotyping of adrenocortical carcinoma: a systematic analysis of published literature 2019–2021

Grisanti

Cosentini

Sigala

et al. 2021

Current Opinion in Oncology

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Purpose of review comprehensive molecular characterization of adrenocortical carcinoma (ACC) through next-generation sequencing and bioinformatics analyses is expanding the number of targets with potential prognostic and therapeutic value. We performed a critical review of recent published literature on genotyping of ACC.Recent findings 423 studies were published between 2019 and 2021. After manual curation we summarized selected evidence in two thematic areas: germline deoxyribonucleic acid (DNA) variations, genomic alterations and prognosis. Summarythe evolving genomic landscape of ACC requires target validation in terms of prognostic and predictive value within scientific consortia. Although the existing multiple driver genes are difficult targets in the perspective of precision oncology, alterations in DNA damage repair genes or in promoter hypermethylation could open new venues for repurposing of existing drugs in ACC.

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“…As the predominant and most prevalent inhibitory neurotransmitter in the central nervous system, γ-aminobutyric acid (GABA) is involved in GABAergic signaling to mediate the synaptic inhibition of neuronal activity in the mammalian brain(2). GABA transmits signals by binding with its receptors, which mainly include GABA A and GABA B receptors(3). The most closely related receptor, the GABA A receptor, is a pentamer assembled from multiple subunits that form a chloride channel(4).…”

Section: Introductionmentioning

confidence: 99%

GABRDpromotes the progression of breast cancer through CDK1-dependent cell cycle regulation

Shang,

Ren,

Feng

et al. 2023

Preprint

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Purpose: Y-aminobutyric acid (GABA) is an important inhibitory amino acid neurotransmitter that exerts its biological function by binding to GABA receptors, which not only play an important role in neuromodulation, but also involved in regulating the development of tumors. Gamma-aminobutyric acid type A receptor subunit delta (GABRD) encodes the delta subunit of GABAA receptor. its impact on breast cancer has not been clearly studied. This study is aiming to reveal the relationship between GABRD and breast cancer development. Methods: We performed a tissue microarray to quantify GABRD expression levels in tumor tissue and paracarcinoma tissue. The regulation of GABRD in the proliferation, migration, and apoptosis of breast cancer was examined by a loss-of-function study. A GeneChip microarray was used to probe GABRD for potential downstream molecules. The interaction between GABRD and CDK1 was verified by a set of functional tests and rescue experiments as well as coimmunoprecipitation. Results: GABRD was expressed at significantly higher levels in tumor tissues and was associated with advanced tumor progression. Silencing GABRD resulted in a significant decrease in proliferation and migration and an increase in apoptosis of breast cancer. GABRD regulated the cell cycle by directly interacting with CDK1, which was identified as an important downstream target. Conclusion: GABRD is a novel breast cancer-related gene and highlights the importance of the GABRD-CDK1 axis in regulating breast cancer proliferation, which provides potential for the development of novel therapeutics.

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A Targeted Bioinformatics Assessment of Adrenocortical Carcinoma Reveals Prognostic Implications of GABA System Gene Expression

Cited by 14 publications

References 146 publications

ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling

ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling

Molecular genotyping of adrenocortical carcinoma: a systematic analysis of published literature 2019–2021

GABRDpromotes the progression of breast cancer through CDK1-dependent cell cycle regulation

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