TRIC-A regulates intracellular Ca2+ homeostasis in cardiomyocytes

Zhou, Xinyu; Li, Ang; Lin, Pei‐Hui; Zhou, Jingsong; Ma, Jianjie

doi:10.1007/s00424-021-02513-6

Cited by 7 publications

(3 citation statements)

References 116 publications

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“…Transmembrane Protein 38A (TMEM38A), also known as trimeric intracellular cation channel type A (TRIC-A) (33), functions as a monovalent cation channel essential for facilitating rapid intracellular calcium release. TRIC-A plays a crucial role in modulating calcium ion transport within cardiac muscle cells (34,35), and its expression is observed during the early stages of zebrafish development (34). ID4 is intricately associated with cancer, with processes such as proliferation, differentiation, migration, and invasion involving numerous cancer types (36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms

Wang,

Mou,

et al. 2024

Front. Endocrinol.

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BackgroundRadiotherapy plays a crucial role in the management of Cervical cancer (CC), as the development of resistance by cancer cells to radiotherapeutic interventions is a significant factor contributing to treatment failure in patients. However, the specific mechanisms that contribute to this resistance remain unclear. Currently, molecular targeted therapy, including mitochondrial genes, has emerged as a new approach in treating different types of cancers, gaining significant attention as an area of research in addressing the challenge of radiotherapy resistance in cancer.MethodsThe present study employed a rigorous screening methodology within the TCGA database to identify a cohort of patients diagnosed with CC who had received radiotherapy treatment. The control group consisted of individuals who demonstrated disease stability or progression after undergoing radiotherapy. In contrast, the treatment group consisted of patients who experienced complete or partial remission following radiotherapy. Following this, we identified and examined the differentially expressed genes (DEGs) in the two cohorts. Subsequently, we conducted additional analyses to refine the set of excluded DEGs by employing the least absolute shrinkage and selection operator regression and random forest techniques. Additionally, a comprehensive analysis was conducted in order to evaluate the potential correlation between the expression of core genes and the extent of immune cell infiltration in patients diagnosed with CC. The mitochondrial-associated genes were obtained from the MITOCARTA 3.0. Finally, the verification of increased expression of the mitochondrial gene TMEM38A in individuals with CC exhibiting sensitivity to radiotherapy was conducted using reverse transcription quantitative polymerase chain reaction and immunohistochemistry assays.ResultsThis process ultimately led to the identification of 7 crucial genes, viz., GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2, which were strongly associated with radiotherapy sensitivity. The enrichment analysis has unveiled a significant association between these 7 crucial genes and prominent signaling pathways, such as the p53 signaling pathway, KRAS signaling pathway, and PI3K/AKT/MTOR pathway. By utilizing these 7 core genes, an unsupervised clustering analysis was conducted on patients with CC, resulting in the categorization of patients into three distinct molecular subtypes. In addition, a predictive model for the sensitivity of CC radiotherapy was developed using a neural network approach, utilizing the expression levels of these 7 core genes. Moreover, the CellMiner database was utilized to predict drugs that are closely linked to these 7 core genes, which could potentially act as crucial agents in overcoming radiotherapy resistance in CC.ConclusionTo summarize, the genes GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2 were found to be closely correlated with the sensitivity of CC to radiotherapy. Notably, TMEM38A, a mitochondrial gene, exhibited the highest degree of correlation, indicating its potential as a crucial biomarker for the modulation of radiotherapy sensitivity in CC.

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Section: Discussionmentioning

confidence: 99%

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms

Wang,

Mou,

et al. 2024

Front. Endocrinol.

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“…However, the regulatory impact in CML is repressive, suggesting different cofactors may be involved. TMEM38A encodes a Ca 2+ channel, enhancing cytosolic Ca 2+ levels [ 59 ]. Consistent with this proposal, CML cells have been shown to contain reduced Ca 2+ levels [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Establishment of the Myeloid TBX-Code Reveals Aberrant Expression of T-Box Gene TBX1 in Chronic Myeloid Leukemia

Nagel,

Haake,

Pommerenke

et al. 2023

IJMS

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T-box genes encode transcription factors, which control developmental processes and promote cancer if deregulated. Recently, we described the lymphoid TBX-code, which collates T-box gene activities in normal lymphopoiesis, enabling identification of members deregulated in lymphoid malignancies. Here, we have extended this analysis to cover myelopoiesis, compiling the myeloid TBX-code and, thus, highlighting which of these genes might be deregulated in myeloid tumor types. We analyzed public T-box gene expression datasets bioinformatically for normal and malignant cells. Candidate T-box-gene-expressing model cell lines were identified and examined by RQ-PCR, Western Blotting, genomic profiling, and siRNA-mediated knockdown combined with RNA-seq analysis and live-cell imaging. The established myeloid TBX-code comprised 10 T-box genes, including progenitor-cell-restricted TBX1. Accordingly, we detected aberrant expression of TBX1 in 10% of stem/progenitor-cell-derived chronic myeloid leukemia (CML) patients. The classic CML cell line K-562 expressed TBX1 at high levels and served as a model to identify TBX1 activators, including transcription factor GATA1 and genomic amplification of the TBX1 locus at 22q11; inhibitors, including BCR::ABL1 fusion and downregulated GNAI2, as well as BMP, FGF2, and WNT signaling; and the target genes CDKN1A, MIR17HG, NAV1, and TMEM38A. The establishment of the myeloid TBX-code permitted identification of aberrant TBX1 expression in subsets of CML patients and cell lines. TBX1 forms an integral part of an oncogenic regulatory network impacting proliferation, survival, and differentiation. Thus, the data spotlight novel diagnostic markers and potential therapeutic targets for this malignancy.

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“…Whereas the ionic homeostasis of cardiac cells is finely tuned by multiple ion channels, transporters, and ionic exchangers in the plasma membrane, the ionic homeostasis of intracellular organelles is also delicately maintained by influx and efflux of different ions. Although it remains debatable in this research field, the potential contribution of the TRIC-A channel in mediating K + influx to ER/SR to counter-balance Ca 2+ release was thoroughly reviewed by Zhou et al [22]. Not only is the ionic homeostasis in cardiac cells essential for normal heart function, but abnormal extracellular ionic concentrations resulting from pathological conditions such as ischemia and renal failure could also promote arrhythmias, which indicates the need for further investigation.…”

mentioning

confidence: 99%

A special issue on calcium dynamics of the heart: remodeling of ion channels and regulatory pathways

Bare

Yue

2021

Pflugers Arch - Eur J Physiol

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TRIC-A regulates intracellular Ca2+ homeostasis in cardiomyocytes

Cited by 7 publications

References 116 publications

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms

Establishment of the Myeloid TBX-Code Reveals Aberrant Expression of T-Box Gene TBX1 in Chronic Myeloid Leukemia

A special issue on calcium dynamics of the heart: remodeling of ion channels and regulatory pathways

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