Reactivation of Atp4a concomitant with intragenic DNA demethylation for cancer inhibition in a gastric cancer model

Cao, Donghui; Zhao, Dan; Jia, Zhifang; Su, Tongrong; Zhang, Yangyu; Wu, Yanhua; Wu, Menghui; Tsukamoto, Tetsuya; Oshima, Masanobu; Jiang, Jing; Cao, Xueyuan

doi:10.1016/j.lfs.2019.117214

Cited by 11 publications

(7 citation statements)

References 32 publications

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“…The factors controlling expression of ATP4A and ATP4B have begun to be characterized. 24,25 ATP4B is necessary for the stability of ATP4A (protein), hence independent expression of ATP4A is unlikely to be physiologically relevant. 26 ATP4B can additionally form a functional pump with the widely expressed non-gastric (colonic) H+/K+ ATPase, ATP12A (HKα2) in experimental models and evidence from knockout mouse models suggests that one alpha isoform may compensate for another.…”

Section: Discussionmentioning

confidence: 99%

“…ATP4A and ATP4B genes are located on different chromosomes, thus disparities in their transcriptional regulation are anticipated. The factors controlling expression of ATP4A and ATP4B have begun to be characterized 24,25 . ATP4B is necessary for the stability of ATP4A (protein), hence independent expression of ATP4A is unlikely to be physiologically relevant 26 .…”

Section: Discussionmentioning

confidence: 99%

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H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients

et al. 2020

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Objectives The gastric H+/K+ ATPase proton pump has previously been shown to be expressed in the human larynx, however its contribution to laryngopharyngeal reflux (LPR) signs, symptoms and associated diseases such as laryngeal cancer is unknown. Proton pump expression in the larynx of patients with LPR and laryngeal cancer was investigated herein. A human hypopharyngeal cell line expressing the proton pump was generated to investigate its effects. Study Design In‐vitro translational. Methods Laryngeal biopsies were obtained from three LPR and eight LSCC patients. ATP4A, ATP4B and HRPT1 were assayed via qPCR. Human hypopharyngeal FaDu cell lines stably expressing proton pump were created using lentiviral transduction and examined via transmission electron microscopy and qPCR for genes associated with inflammation or laryngeal cancer. Results Expression of ATP4A and ATP4B was detected in 3/3 LPR, 4/8 LSCC‐tumor and 3/8 LSCC‐adjacent specimens. Expression of ATP4A and ATP4B in FaDu elicited mitochondrial damage and expression of IL1B, PTGS2, and TNFA (P < .0001); expression of ATP4B alone did not. Conclusions Gastric proton pump subunits are expressed in the larynx of LPR and LSCC patients. Mitochondrial damage and changes in gene expression observed in cells expressing the full proton pump, absent in those expressing a single subunit, suggest that acid secretion by functional proton pumps expressed in upper airway mucosa may elicit local cell and molecular changes associated with inflammation and cancer. Level of Evidence NA Laryngoscope, 131:130–135, 2021

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients

et al. 2020

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“…Through in vivo and in vitro experiments in animals and humans, researchers have found that ATP4A and ATP4B were partially or fully methylated in gastric cancer cells. It was also verified that the reactivation and demethylation of ATP4A and ATP4B can effectively inhibit the progression of gastric cancer ( Lin et al, 2017 ; Cao et al, 2020 ). Hence, ATP4A and ATP4B are important tumor suppressor genes.…”

Section: Discussionmentioning

confidence: 87%

ESRRG, ATP4A, and ATP4B as Diagnostic Biomarkers for Gastric Cancer: A Bioinformatic Analysis Based on Machine Learning

et al. 2022

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Based on multiple bioinformatics methods and machine learning techniques, this study was designed to explore potential hub genes of gastric cancer with a diagnostic value. The novel biomarkers were detected through multiple databases of gastric cancer–related genes. The NCBI Gene Expression Omnibus (GEO) database was used to obtain gene expression files. Three hub genes (ESRRG, ATP4A, and ATP4B) were detected through a combination of weighted gene co-expression network analysis (WGCNA), gene–gene interaction network analysis, and supervised feature selection method. GEPIA2 was used to verify the differences in the expression levels of the hub genes in normal and cancer tissues in the RNA-seq levels of Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. The objectivity of potential hub genes was also verified by immunohistochemistry in the Human Protein Atlas (HPA) database and transcription factor–hub gene regulatory network. Machine learning (ML) methods including data pre-processing, model selection and cross-validation, and performance evaluation were examined on the hub-gene expression profiles in five Gene Expression Omnibus datasets and verified on a GEO external validation (EV) dataset. Six supervised learning models (support vector machine, random forest, k-nearest neighbors, neural network, decision tree, and eXtreme Gradient Boosting) and one semi-supervised learning model (label spreading) were established to evaluate the diagnostic value of biomarkers. Among the six supervised models, the support vector machine (SVM) algorithm was the most effective one according to calculated performance metrics, including 0.93 and 0.99 area under the curve (AUC) scores on the test and external validation datasets, respectively. Furthermore, the semi-supervised model could also successfully learn and predict sample types, achieving a 0.986 AUC score on the EV dataset, even when 10% samples in the five GEO datasets were labeled. In conclusion, three hub genes (ATP4A, ATP4B, and ESRRG) closely related to gastric cancer were mined, based on which the ML diagnostic model of gastric cancer was conducted.

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“…6 C). ATP4A is responsible for H + excretion in exchange for K + ion at the expense of ATP consumption in cells [ 71 ]. To our knowledge, K + ion is an essential osmolyte for maintaining a high intracellular osmolarity in the cell [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Osmoregulatory strategies of estuarine fish Scatophagus argus in response to environmental salinity changes

Liu

Zhang

et al. 2022

BMC Genomics

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Background Scatophagus argus, an estuarine inhabitant, can rapidly adapt to different salinity environments. However, the knowledge of the molecular mechanisms underlying its strong salinity tolerance remains unclear. The gill, as the main osmoregulatory organ, plays a vital role in the salinity adaptation of the fish, and thus relative studies are constructive to reveal unique osmoregulatory mechanisms in S. argus. Results In the present study, iTRAQ coupled with nanoLC-MS/MS techniques were employed to explore branchial osmoregulatory mechanisms in S. argus acclimated to different salinities. Among 1,604 identified proteins, 796 differentially expressed proteins (DEPs) were detected. To further assess osmoregulatory strategies in the gills under different salinities, DEPs related to osmoregulatory (22), non-directional (18), hypo- (52), and hypersaline (40) stress responses were selected. Functional annotation analysis of these selected DEPs indicated that the cellular ion regulation (e.g. Na+-K+-ATPase [NKA] and Na+-K+-2Cl− cotransporter 1 [NKCC1]) and ATP synthesis were deeply involved in the osmoregulatory process. As an osmoregulatory protein, NKCC1 expression was inhibited under hyposaline stress but showed the opposite trend in hypersaline conditions. The expression levels of NKA α1 and β1 were only increased under hypersaline challenge. However, hyposaline treatments could enhance branchial NKA activity, which was inhibited under hypersaline environments, and correspondingly, reduced ATP content was observed in gill tissues exposed to hyposaline conditions, while its contents were increased in hypersaline groups. In vitro experiments indicated that Na+, K+, and Cl− ions were pumped out of branchial cells under hypoosmotic stress, whereas they were absorbed into cells under hyperosmotic conditions. Based on our results, we speculated that NKCC1-mediated Na+ influx was inhibited, and proper Na+ efflux was maintained by improving NKA activity under hyposaline stress, promoting the rapid adaptation of branchial cells to the hyposaline condition. Meanwhile, branchial cells prevented excessive loss of ions by increasing NKA internalization and reducing ATP synthesis. In contrast, excess ions in cells exposed to the hyperosmotic medium were excreted with sufficient energy supply, and reduced NKA activity and enhanced NKCC1-mediated Na+ influx were considered a compensatory regulation. Conclusions S. argus exhibited divergent osmoregulatory strategies in the gills when encountering hypoosmotic and hyperosmotic stresses, facilitating effective adaptabilities to a wide range of environmental salinity fluctuation.

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Reactivation of Atp4a concomitant with intragenic DNA demethylation for cancer inhibition in a gastric cancer model

Cited by 11 publications

References 32 publications

H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients

H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients

ESRRG, ATP4A, and ATP4B as Diagnostic Biomarkers for Gastric Cancer: A Bioinformatic Analysis Based on Machine Learning

Osmoregulatory strategies of estuarine fish Scatophagus argus in response to environmental salinity changes

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