Integrative Transcriptomic, Proteomic and Functional Analysis Reveals ATP1B3 as a Diagnostic and Potential Therapeutic Target in Hepatocellular Carcinoma

Lu, Shanshan; Cai, Shenglan; Xu, Peng; Cheng, Ruochan; Zhang, Yiya

doi:10.3389/fimmu.2021.636614

Cited by 15 publications

(14 citation statements)

References 70 publications

(84 reference statements)

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“…β3 is involved in cell proliferation through the PI3K/AKT (phosphatidylinositol 3-kinase/protein kinase B) signaling pathway, and cells in which β3 is knocked down tend to undergo apoptosis ( Li et al , 2017 ). Similar reports on hepatocellular carcinoma suggest that β3 may be a biomarker for prognostic prediction ( Lu et al , 2021 ). These reports suggest that β3 may play a role during the adaptation of cells to environments that differ from the in vivo environment or that require higher energy efficiency.…”

Section: Discussionsupporting

confidence: 59%

Na+/K+ ATPase α1 and β3 subunits are localized to the basolateral membrane of trophectoderm cells in human blastocysts

et al. 2022

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STUDY QUESTION Is there a relation between specific Na+/K+ ATPase isoform expression and localization in human blastocysts and the developmental behavior of the embryo? SUMMARY ANSWER Na+/K+ ATPase α1, β1 and β3 are the main isoforms expressed in human blastocysts and no association was found between the expression level of their respective mRNAs and the rate of blastocyst expansion. WHAT IS KNOWN ALREADY In mouse embryos, Na+/K+ ATPase α1 and β1 are expressed in the basolateral membrane of trophectoderm (TE) cells and are believed to be involved in blastocoel formation (cavitation). STUDY DESIGN, SIZE, DURATION A total of 20 surplus embryos from 11 patients who underwent IVF and embryo transfer at a university hospital between 2009 and 2018 were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS After freezing and thawing Day 5 human blastocysts, their developmental behavior was observed for 24 h using time-lapse imaging, and the expression of Na+/K+ ATPase isoforms was examined using quantitative RT-PCR (RT-qPCR). The expressed isoforms were then localized in blastocysts using fluorescent immunostaining. MAIN RESULTS AND THE ROLE OF CHANCE RT-qPCR results demonstrated the expression of Na+/K+ ATPase α1, β1 and β3 isoforms in human blastocysts. Isoforms α1 and β3 were localized to the basolateral membrane of TE cells, and β1 was localized between TE cells. A high level of β3 mRNA expression correlated with easier hatching (P = 0.0261). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The expression of mRNA and the localization of proteins of interest were verified, but we have not been able to perform functional analysis. WIDER IMPLICATIONS OF THE FINDINGS Of the various Na+/K+ ATPase isoforms, expression levels of the α1, β1 and β3 mRNAs were clearly higher than other isoforms in human blastocysts. Since α1 and β3 were localized to the basolateral membrane via fluorescent immunostaining, we believe that these subunits contribute to the dilation of the blastocoel. The β1 isoform is localized between TE cells and may be involved in tight junction formation, as previously reported in mouse embryos. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the JSPS KAKENHI (https://www.jsps.go.jp/english/index.html), grant number 17K11215. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts of interest.

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Section: Discussionsupporting

confidence: 59%

Na+/K+ ATPase α1 and β3 subunits are localized to the basolateral membrane of trophectoderm cells in human blastocysts

et al. 2022

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“…Na+/K+-ATPase (NKA) has been proposed as a signal transducer involved in various pathobiological processes, including hepatocellular carcinoma (HCC) ( 33 ). We identified an enrichment of the ATP1B1 an astrocyte-specific isoform of the Na+/K+-ATPase transmembrane ionic pump, by RNA sequencing analysis of endothelial cells from a mouse liver fibrosis model ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

“…To date, 4 NKA a-subunits (a1, a2, a3, and a4) and 4 b-subunits (b1, b2, b3, and b4) have been identified. Abnormal NKA can lead to a variety of diseases, including hypokalemic periodic paralysis and CNS symptoms ( 47 ), cardiovascular disorders ( 48 ), atherosclerosis ( 49 ), Alzheimer’s disease ( 50 ), and hepatocellular carcinoma (HCC) ( 33 ). ATP1B1 is downregulated in human epithelial cancer cells ( 51 – 53 ).…”

Section: Discussionmentioning

confidence: 99%

Trimethylamine-N-oxide (TMAO) mediates the crosstalk between the gut microbiota and hepatic vascular niche to alleviate liver fibrosis in nonalcoholic steatohepatitis

et al. 2022

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Liver fibrosis is one main histological characteristic of nonalcoholic steatohepatitis (NASH), a disease paralleling a worldwide surge in metabolic syndromes with no approved therapies. The role of the gut microbiota in NASH pathogenesis has not been thoroughly illustrated, especially how the gut microbiota derives metabolites to influence the distal liver in NASH. Here, we performed 16S rDNA amplicon sequencing analysis of feces from a mouse NASH model induced by a Western diet and CCl4 injury and found genera under Streptococcaceae, Alcaligenaceae, Oscillibacter, and Pseudochrobactrum, which are related metabolites of TMAO. Injection of the gut microbial metabolite TMAO reduced the progression of liver fibrosis in the mouse NASH model. Further analysis revealed that the anti-fibrotic TMAO normalized gut microbiota diversity and preserved liver sinusoidal endothelial cell integrity by inhibiting endothelial beta 1-subunit of Na (+), K (+)-ATPase (ATP1B1) expression. Collectively, our findings suggest TMAO-mediated crosstalk between microbiota metabolites and hepatic vasculature, and perturbation of this crosstalk disrupts sinusoidal vasculature to promote liver fibrosis in NASH.

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“…In addition, several other PSGs ( ATP1B3 , TFDP2 , GK5 , XRN1 , PEX5L , USP13 , NDUFB5 , MRPL47 , ACTL6A , KIF26B , CDKL5 , and HDAC4 ) were identified by other four selective signal analyses and DCMS ( Supplementary Figures S4, S5 ). ATP1B3 is related to immune cell infiltration and immune-related cytokines expression in hepatocellular carcinoma ( Lu et al, 2021 ). TFDP2 affects angiogenesis, nephrogenesis, and kidney metabolic function ( Köttgen et al, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

Genomic Analyses for Selective Signatures and Genes Involved in Hot Adaptation Among Indigenous Chickens From Different Tropical Climate Regions

Liu

Yang

et al. 2022

Front. Genet.

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Climate change, especially weather extremes like extreme cold or extreme hot, is a major challenge for global livestock. One of the animal breeding goals for sustainable livestock production should be to breed animals with excellent climate adaptability. Indigenous livestock and poultry are well adapted to the local climate, and they are good resources to study the genetic footprints and mechanism of the resilience to weather extremes. In order to identify selection signatures and genes that might be involved in hot adaptation in indigenous chickens from different tropical climates, we conducted a genomic analysis of 65 indigenous chickens that inhabit different climates. Several important unique positively selected genes (PSGs) were identified for each local chicken group by the cross-population extended haplotype homozygosity (XP-EHH). These PSGs, verified by composite likelihood ratio, genetic differentiation index, nucleotide diversity, Tajima’s D, and decorrelated composite of multiple signals, are related to nerve regulation, vascular function, immune function, lipid metabolism, kidney development, and function, which are involved in thermoregulation and hot adaptation. However, one common PSG was detected for all three tropical groups of chickens via XP-EHH but was not confirmed by other five types of selective sweep analyses. These results suggest that the hot adaptability of indigenous chickens from different tropical climate regions has evolved in parallel by taking different pathways with different sets of genes. The results from our study have provided reasonable explanations and insights for the rapid adaptation of chickens to diverse tropical climates and provide practical values for poultry breeding.

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Integrative Transcriptomic, Proteomic and Functional Analysis Reveals ATP1B3 as a Diagnostic and Potential Therapeutic Target in Hepatocellular Carcinoma

Cited by 15 publications

References 70 publications

Na+/K+ ATPase α1 and β3 subunits are localized to the basolateral membrane of trophectoderm cells in human blastocysts

Na+/K+ ATPase α1 and β3 subunits are localized to the basolateral membrane of trophectoderm cells in human blastocysts

Trimethylamine-N-oxide (TMAO) mediates the crosstalk between the gut microbiota and hepatic vascular niche to alleviate liver fibrosis in nonalcoholic steatohepatitis

Genomic Analyses for Selective Signatures and Genes Involved in Hot Adaptation Among Indigenous Chickens From Different Tropical Climate Regions

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