ASPH Regulates Osteogenic Differentiation and Cellular Senescence of BMSCs

Peng, Hui; Guo, Qi; Xiao, Ye; Su, Tian; Tong, Jiang; Guo, Lijuan; Wang, Min

doi:10.3389/fcell.2020.00872

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…GSK3β is widely recognized as a downstream target of AKT 20 , and previous studies have shown that inhibition of ASPH enzymatic activity leads to increased GSK3β phosphorylation, which promotes tumor cell senescence 21 , 22 . This interaction was also examined in our study, but ASPH inhibitors did not induce GSK3β phosphorylation, suggesting that they may not induce senescence in the cell lines we examined.…”

Section: Resultsmentioning

confidence: 99%

Heterogeneous Response of Tumor Cell Lines to Inhibition of Aspartate β-hydroxylase

Kanwal,

Polakova,

Olsen

et al. 2024

J. Cancer

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Background : Cancer development involves alterations in key cellular pathways, with aspartate β-hydroxylase (ASPH) emerging as an important player in tumorigenesis. ASPH is upregulated in various cancer types, where it promotes cancer progression mainly by regulating the Notch1 and SRC pathways. Methods : This study explored the responses of various human cervical, pharyngeal, and breast tumor cell lines to second- and third-generation ASPH inhibitors (MO-I-1151 and MO-I-1182) using proliferation, migration, and invasion assays; western blotting; and cell cycle analysis. Results : ASPH inhibition significantly reduced cell proliferation, migration, and invasion and disrupted both the canonical and noncanonical Notch1 pathways. The noncanonical pathway was particularly mediated by AKT signaling. Cell cycle analysis revealed a marked reduction in cyclin D1 expression, further confirming the inhibitory effect of ASPH inhibitors on cell proliferation. Additional analysis revealed G0/G1 arrest and restricted progression into S phase, highlighting the regulatory impact of ASPH inhibitors on the cell cycle. Furthermore, ASPH inhibition induced distinctive alterations in nuclear morphology. The high heterogeneity in the responses of individual tumor cell lines to ASPH inhibitors, both quantitatively and qualitatively, underscores the complex network of mechanisms that are regulated by ASPH and influence the efficacy of ASPH inhibition. The effects of ASPH inhibitors on Notch1 pathway activity, cyclin D1 expression, and nuclear morphology contribute to the understanding of the multifaceted effects of these inhibitors on cancer cell behavior. Conclusion : This study not only suggests that ASPH inhibitors are effective against tumor cell progression, in part through the induction of cell cycle arrest, but also highlights the diverse and heterogeneous effects of these inhibitors on the behavior of tumor cells of different origins.

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Section: Resultsmentioning

confidence: 99%

Heterogeneous Response of Tumor Cell Lines to Inhibition of Aspartate β-hydroxylase

Kanwal,

Polakova,

Olsen

et al. 2024

J. Cancer

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“…Of these, bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into various types of cells, including osteoblast, and are found in various tissues including bone marrow, adipose tissue, umbilical cord blood, and cancellous bone [ 32 ]. Because of its high proliferation capacity, it is possible to directly perform cell transplantation or implantation on biological material to repair the defect of tissue.…”

Section: Discussionmentioning

confidence: 99%

Effect of silk fibroin scaffold loaded with 17-β estradiol on the proliferation and differentiation of BMSCs

Bai

Wang

et al. 2023

Regenerative Therapy

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“…Differential expression analysis was performed between the two groups of camels using the DESeq2 package in R (version 4.2.1), based on negative binomial distribution. Considering previous studies ( 19 , 20 ) and our specific experimental situation, adjusted p -values ( p adjust ) < 0.01 and |log2FoldChange| >2 were established as the thresholds for significance. p -values were adjusted for multiple testing using the Benjamini and Hochberg methods.…”

Section: Methodsmentioning

confidence: 99%

Transcriptome analysis to identify candidate genes related to mammary gland development of Bactrian camel (Camelus bactrianus)

et al. 2023

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IntroductionThe demand for camel milk, which has unique therapeutic properties, is increasing. The mammary gland is the organ in mammals responsible for the production and quality of milk. However, few studies have investigated the genes or pathways related to mammary gland growth and development in Bactrian camels. This study aimed to compare the morphological changes in mammary gland tissue and transcriptome expression profiles between young and adult female Bactrian camels and to explore the potential candidate genes and signaling pathways related to mammary gland development.MethodsThree 2 years-old female camels and three 5 years-old adult female camels were maintained in the same environment. The parenchyma of the mammary gland tissue was sampled from the camels using percutaneous needle biopsy. Morphological changes were observed using hematoxylin-eosin staining. High-throughput RNA sequencing was performed using the Illumina HiSeq platform to analyze changes in the transcriptome between young and adult camels. Functional enrichment, pathway enrichment, and protein–protein interaction networks were also analyzed. Gene expression was verified using quantitative real-time polymerase chain reaction (qRT-PCR).ResultsHistomorphological analysis showed that the mammary ducts and mammary epithelial cells in adult female camels were greatly developed and differentiated from those in young camels. Transcriptome analysis showed that 2,851 differentially expressed genes were obtained in the adult camel group compared to the young camel group, of which 1,420 were upregulated, 1,431 were downregulated, and 2,419 encoded proteins. Functional enrichment analysis revealed that the upregulated genes were significantly enriched for 24 pathways, including the Hedgehog signaling pathway which is closely related to mammary gland development. The downregulated genes were significantly enriched for seven pathways, among these the Wnt signaling pathway was significantly related to mammary gland development. The protein–protein interaction network sorted the nodes according to the degree of gene interaction and identified nine candidate genes: PRKAB2, PRKAG3, PLCB4, BTRC, GLI1, WIF1, DKK2, FZD3, and WNT4. The expression of fifteen genes randomly detected by qRT-PCR showed results consistent with those of the transcriptome analysis.DiscussionPreliminary findings indicate that the Hedgehog, Wnt, oxytocin, insulin, and steroid biosynthesis signaling pathways have important effects on mammary gland development in dairy camels. Given the importance of these pathways and the interconnections of the involved genes, the genes in these pathways should be considered potential candidate genes. This study provides a theoretical basis for elucidating the molecular mechanisms associated with mammary gland development and milk production in Bactrian camels.

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ASPH Regulates Osteogenic Differentiation and Cellular Senescence of BMSCs

Cited by 10 publications

References 46 publications

Heterogeneous Response of Tumor Cell Lines to Inhibition of Aspartate β-hydroxylase

Heterogeneous Response of Tumor Cell Lines to Inhibition of Aspartate β-hydroxylase

Effect of silk fibroin scaffold loaded with 17-β estradiol on the proliferation and differentiation of BMSCs

Transcriptome analysis to identify candidate genes related to mammary gland development of Bactrian camel (Camelus bactrianus)

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