SLC4A7 and mTORC1 raise nucleotide synthesis with bicarbonate

Koe, Jessica C.; Hewton, Keeley G.; Parker, Seth J.

doi:10.1016/j.molcel.2022.08.010

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…Interestingly, it is heavily connected to several lncRNAs in the brown4 network. SLC4A7 is also a target of mTORC1 signaling and sustains the mTORC1-dependent control of nucleotide synthesis [48,49]. Moreover, SLC4A7 has also been reported to promote EMT and metastasis of the head and neck squamous cell carcinoma; similarly, pHi dynamics studies as well as mRNA and protein expression of acid-base transporters among breast cancer patients showed that increased SLC4A7 expression predicts proliferative activity and metastasis [50,51].…”

Section: Discussionmentioning

confidence: 97%

Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System

Fustaino,

Papoff,

Ruberti

et al. 2024

IJMS

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We investigated mRNA-lncRNA co-expression patterns in a cellular model system of non-small cell lung cancer (NSCLC) sensitive and resistant to the epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib/gefitinib. The aim of this study was to unveil insights into the complex mechanisms of NSCLC targeted therapy resistance and epithelial-to-mesenchymal transition (EMT). Genome-wide RNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs and lncRNAs. Functional enrichment analysis and identification of lncRNAs were conducted on modules associated with the EGFR-TKI response and/or intermediate EMT phenotypes. We constructed lncRNA-mRNA co-expression networks and identified key modules and their enriched biological functions. Processes enriched in the selected modules included RHO (A, B, C) GTPase and regulatory signaling pathways, apoptosis, inflammatory and interleukin signaling pathways, cell adhesion, cell migration, cell and extracellular matrix organization, metabolism, and lipid metabolism. Interestingly, several lncRNAs, already shown to be dysregulated in cancer, are connected to a small number of mRNAs, and several lncRNAs are interlinked with each other in the co-expression network.

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Section: Discussionmentioning

confidence: 97%

Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System

Fustaino,

Papoff,

Ruberti

et al. 2024

IJMS

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“…SLC4A7 is essential for encoding the sodium bicarbonate cotransporter, 28 influences the adjustment of intracellular pH drawn into visual and auditory sensory transfer and may be associated with susceptibility to cancer and cancer severity. 5,6,29 However, genome-wide association studies have extensively examined the association between the SLC4A7 rs4973768 polymorphism and breast cancer risk and reported inconsistent results. 17,30–32 Therefore, we used a meta-analysis to more precisely explore the correlation.…”

Section: Discussionmentioning

confidence: 99%

Update on the relationship between the SLC4A7 variant rs4973768 and breast cancer risk: a systematic review and meta-analysis

Zhou

Sun

2023

J Int Med Res

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Objective This meta-analysis aimed to update knowledge about the association between the SLC4A7 variant rs4973768 and breast cancer incidence. Methods Studies were identified from relevant digital databases. Fixed- or random-effects models were used to calculate odds ratios and 95% confidence intervals. Statistical Q and I2 tests and sensitivity analyses were used to detect interstudy heterogeneity and test the statistical stability of overall estimates, respectively. Egger’s tests were applied to detect publication bias among included studies. In silico analysis was used to ascertain increased expression of SLC4A7 mRNA in rs4973768 with the mutant allele. Trial sequential analysis was used to calculate the study’s sample size. Results The overall odds ratios reflected a positive correlation between the SLC4A7 rs4973768 polymorphism and susceptibility to breast cancer in five genetic comparisons of alleles T and C, and tests revealed significant heterogeneity in the allele comparison. After stratification by ethnicity, heterogeneity in Asian and White populations substantially decreased (Ph = 0.984, I2 = 0%) and remained stable (Ph = 0.083, I2 = 46.3%), respectively. The mutant allele was associated with increased expression of SLC4A7 mRNA in rs4973768. The cumulative z curve indicated that our conclusions were robust. Conclusions Our updated consequence shows that the SLC4A7 rs4973768 polymorphism is associated with increased breast cancer risk.

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Potential Theranostic Roles of SLC4 Molecules in Human Diseases

Zhong,

Dong,

Ruan

et al. 2023

IJMS

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The solute carrier family 4 (SLC4) is an important protein responsible for the transport of various ions across the cell membrane and mediating diverse physiological functions, such as the ion transporting function, protein-to-protein interactions, and molecular transduction. The deficiencies in SLC4 molecules may cause multisystem disease involving, particularly, the respiratory system, digestive, urinary, endocrine, hematopoietic, and central nervous systems. Currently, there are no effective strategies to treat these diseases. SLC4 proteins are also found to contribute to tumorigenesis and development, and some of them are regarded as therapeutic targets in quite a few clinical trials. This indicates that SLC4 proteins have potential clinical prospects. In view of their functional characteristics, there is a critical need to review the specific functions of bicarbonate transporters, their related diseases, and the involved pathological mechanisms. We summarize the diseases caused by the mutations in SLC4 family genes and briefly introduce the clinical manifestations of these diseases as well as the current treatment strategies. Additionally, we illustrate their roles in terms of the physiology and pathogenesis that has been currently researched, which might be the future therapeutic and diagnostic targets of diseases and a new direction for drug research and development.

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SLC4A7 and mTORC1 raise nucleotide synthesis with bicarbonate

Cited by 3 publications

References 10 publications

Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System

Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System

Update on the relationship between the SLC4A7 variant rs4973768 and breast cancer risk: a systematic review and meta-analysis

Potential Theranostic Roles of SLC4 Molecules in Human Diseases

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