Fam83d modulates MAP kinase and AKT signaling and is induced during neurogenic skeletal muscle atrophy

Cooper, Lisa M.; Hanson, Abby; Kavanagh, Jack A.; Waddell, David

doi:10.1016/j.cellsig.2020.109576

Cited by 10 publications

(4 citation statements)

References 31 publications

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“…Akt, also known as protein kinase B, plays critical roles in many cell activities. Recent research also found that Akt signaling was involved in skeletal muscle cell responses to denervation (30,31) . Strong interaction between Akt signaling and Cx43 was found in many other diseases models (14,19,32,33) , and previous evidences indicated they shared mutually inhibiting relationship.…”

Section: Discussionmentioning

confidence: 99%

Negative Effects of Cx43 during Denervated Skeletal Muscle Atrophy can be Attenuated by Blueberry Extracts via Regulating Akt Pathway

Huang

Zhang

You

et al. 2022

Preprint

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Background: Lack of effective treatment for alleviating the irreversible skeletal muscle atrophy caused by peripheral nerve disfunction has long been a clinical problem. For seeking therapeutic targets, several signaling pathways in muscle cells that activated by denervation have been explored. Important roles of Cx43 in other types of pathologic processes such as have been reported. Methods: Denervation mice model was created. Hematoxylin–Eosin (HE) and immunofluorescence staining were applied and analyzed. Western blot and quantitative real-time PCR (qPCR) were used. All statistical testing was performed by t test.Results: Our study investigated the negative role of Cx43 during muscle cells degeneration after denervation. Blueberry extracts was applied orally and its protective effect for denervated skeletal muscle atrophy was found in our study, and we demonstrated that Cx43/Akt pathway in denervated muscle cells was modulated by blueberry extracts. Conclusion: Negative effects of Cx43 during denervated skeletal muscle atrophy can be attenuated by blueberry extracts via regulating Akt pathway.

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Section: Discussionmentioning

confidence: 99%

Negative Effects of Cx43 during Denervated Skeletal Muscle Atrophy can be Attenuated by Blueberry Extracts via Regulating Akt Pathway

Huang

Zhang

You

et al. 2022

Preprint

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“…Scored as 9, Fam83d on Chr 2 is known to be involved in the positive regulation of cell cycle G1/S phase transition, protein localization to the mitotic spindle, and regulation of intracellular signal transduction. Fam83d is expressed in skeletal muscle and is significantly induced in response to denervation and neurogenic atrophy involving MAP kinase and AKT/PKB (protein kinase B) signaling ( 44 ). However, there are very few studies pertaining to this gene and it needs to be explored further in the context of cardiac Cu-related associations identified.…”

Section: Discussionmentioning

confidence: 99%

Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and functional analyses using BXD family mice

Bajpai

Orgil

et al. 2023

Front. Cardiovasc. Med.

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BackgroundCopper (Cu) is essential for the functioning of various enzymes involved in important cellular and physiological processes. Although critical for normal cardiac function, excessive accumulation, or deficiency of Cu in the myocardium is detrimental to the heart. Fluctuations in cardiac Cu content have been shown to cause cardiac pathologies and imbalance in systemic Cu metabolism. However, the genetic basis underlying cardiac Cu levels and their effects on heart traits remain to be understood. Representing the largest murine genetic reference population, BXD strains have been widely used to explore genotype-phenotype associations and identify quantitative trait loci (QTL) and candidate genes.MethodsCardiac Cu concentration and heart function in BXD strains were measured, followed by QTL mapping. The candidate genes modulating Cu homeostasis in mice hearts were identified using a multi-criteria scoring/filtering approach.ResultsSignificant correlations were identified between cardiac Cu concentration and left ventricular (LV) internal diameter and volumes at end-diastole and end-systole, demonstrating that the BXDs with higher cardiac Cu levels have larger LV chamber. Conversely, cardiac Cu levels negatively correlated with LV posterior wall thickness, suggesting that lower Cu concentration in the heart is associated with LV hypertrophy. Genetic mapping identified six QTLs containing a total of 217 genes, which were further narrowed down to 21 genes that showed a significant association with cardiac Cu content in mice. Among those, Prex1 and Irx3 are the strongest candidates involved in cardiac Cu modulation.ConclusionCardiac Cu level is significantly correlated with heart chamber size and hypertrophy phenotypes in BXD mice, while being regulated by multiple genes in several QTLs. Prex1 and Irx3 may be involved in modulating Cu metabolism and its downstream effects and warrant further experimental and functional validations.

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“…It has previously been reported that FAM83D is involved in various complex biological processes, including cell proliferation, apoptosis, and invasion (Cooper et al, 2020;Yin et al, 2020;Yu et al, 2020). In addition, emerging studies have suggested a functional link between FAM83D and tumor development (Meng et al, 2021;Zhao et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer and single-cell analysis reveals FAM83D expression as a cancer prognostic biomarker

Chen

Wang

et al. 2022

Front. Genet.

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Background: The family with sequence similarity 83 member D (FAM83D) protein is known to play a significant role in many human diseases. However, its role in cancer remains ambiguous. This study aimed to investigate the function of FAM83D in a pan-cancer analysis, with a special focus on breast cancer.Methods: Samples were collected from The Cancer Genome Atlas (TCGA) and used for bioinformatic analysis. Datasets from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx) databases were also analyzed for verification. The potential value of FAM83D as a prognostic and diagnostic biomarker was visualized through R software. The “survival” and “GSVA” package were used for univariate, multivariate and pathway enrichment analyseis. We further analyzed the CancerSEA databases and TISIDB websites for single-cell and immune-related profiling. Lastly, we validated those data in vitro using quantitative reverse transcriptase-polymerase chain reaction (RT‒qPCR), cell counting kit-8 (CCK-8), transwell, flow cytometry, and tumorigenicity assays in a murine cell line model.Results: The expression of FAM83D in tumor samples was significantly higher than in normal tissues for most cancer types in the datasets. We confirmed this finding using RT‒qPCR in a breast cancer cell line. Analysis of multiple datasets suggests that overall survival (OS) was extremely poor for breast cancer patients with high FAM83D expression. The CCK-8 assay demonstrated that MCF-7 cell proliferation was inhibited after genetic silencing of FAM83D. Transwell assay showed that knockdown of FAM83D significantly inhibited the invasion and migration ability of MCF-7 cells compared to the control. The results of flow cytometry showed that silencing FAM83D could block the G1 phase of MCF-7 cells compared with negative groups. The tumorigenicity assay in nude mice indicated that the tumorigenic ability to silence FAM83D decreased compared.Conclusion: Results suggest that FAM83D expression can serve as a valuable biomarker and core gene across cancer types. Furthermore, FAM83D expression is significantly associated with MCF-7 cell proliferation and thus may be a prospective prognostic biomarker especially for breast cancer.

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Fam83d modulates MAP kinase and AKT signaling and is induced during neurogenic skeletal muscle atrophy

Cited by 10 publications

References 31 publications

Negative Effects of Cx43 during Denervated Skeletal Muscle Atrophy can be Attenuated by Blueberry Extracts via Regulating Akt Pathway

Negative Effects of Cx43 during Denervated Skeletal Muscle Atrophy can be Attenuated by Blueberry Extracts via Regulating Akt Pathway

Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and functional analyses using BXD family mice

Pan-cancer and single-cell analysis reveals FAM83D expression as a cancer prognostic biomarker

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