BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

Li, Jianhui; Tian, Xiaojuan; Nie, Ye; He, Ying; Wu, Wenlong; Lei, Xinjun; Zhang, Tianchen; Wang, Yanfang; Mao, Zhenzhen; Hong, Zhiwu; Zhang, Xuan; Song, Wenjie

doi:10.3389/fmolb.2021.762541

Cited by 8 publications

(5 citation statements)

References 39 publications

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“…BTBD10 was known to activate AKT by inhibiting PP2A-mediated dephosphorylation and inactivation of AKT [ 52 ]. Studies have reported that BTBD10 is a prognostic biomarker in cancer and associated with immune infiltration such as glioma [ 53 ], and hepatocellular carcinoma [ 54 , 55 ]. Furthermore, a decrease in BTBD10 expression has been linked to motor neuron death in cases of amyotrophic lateral sclerosis cases due to the downregulation of the AKT-mediated prosurvival signal [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Single-cell and bulk RNA-seq unveils the immune infiltration landscape associated with cuproptosis in cerebral cavernous malformations

Chen,

Bao,

et al. 2024

Biomark Res

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Background Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development. Methods Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs. Results Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis. Conclusion This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes—PFDN4, CEMIP, and BTBD10—may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs.

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Section: Discussionmentioning

confidence: 99%

Single-cell and bulk RNA-seq unveils the immune infiltration landscape associated with cuproptosis in cerebral cavernous malformations

Chen,

Bao,

et al. 2024

Biomark Res

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“…It has been identified as an EMT and metastasis regulator in NPC ( 34 ) and NSCLC ( 35 ). BTBD10 functions as an activator of AKT family members by inhibiting PPP2CA-mediated dephosphorylation, and a few studies have identified it as a prognostic risk factor in hepatocellular carcinoma ( 36 ) and glioma ( 37 ). DLX1 serves as a two-sided transcriptional regulator of the TGF-β superfamily that may be either an oncogene or a suppressor in different types of tumors ( 38 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis signature and PLCD3 predicts immune infiltration and drug responses in osteosarcoma

Yin

Jiang

et al. 2023

Front. Oncol.

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Osteosarcoma (OS) is a cancer that is frequently found in children and adolescents and has made little improvement in terms of prognosis in recent years. A recently discovered type of programmed cell death called cuproptosis is mediated by copper ions and the tricarboxylic acid (TCA) cycle. The expression patterns, roles, and prognostic and predictive capabilities of the cuproptosis regulating genes were investigated in this work. TARGET and GEO provided transcriptional profiling of OS. To find different cuproptosis gene expression patterns, consensus clustering was used. To identify hub genes linked to cuproptosis, differential expression (DE) and weighted gene co-expression network analysis (WGCNA) were used. Cox regression and Random Survival Forest were used to build an evaluation model for prognosis. For various clusters/subgroups, GSVA, mRNAsi, and other immune infiltration experiments were carried out. The drug-responsive study was carried out by the Oncopredict algorithm. Cuproptosis genes displayed two unique patterns of expression, and high expression of FDX1 was associated with a poor outcome in OS patients. The TCA cycle and other tumor-promoting pathways were validated by the functional study, and activation of the cuproptosis genes may also be connected with immunosuppressive state. The robust survival prediction ability of a five-gene prognostic model was verified. This rating method also took stemness and immunosuppressive characteristics into account. Additionally, it can be associated with a higher sensitivity to medications that block PI3K/AKT/mTOR signaling as well as numerous chemoresistances. U2OS cell migration and proliferation may be encouraged by PLCD3. The relevance of PLCD3 in immunotherapy prediction was verified. The prognostic significance, expressing patterns, and functions of cuproptosis in OS were revealed in this work on a preliminary basis. The cuproptosis-related scoring model worked well for predicting prognosis and chemoresistance.

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“…In vitro analysis has demonstrated that BTBD10 interacts with protein phosphatase 2A (PP2A) and inhibits the dephosphorylation of AKTs by PP2A, which indicates that BTBD10 can interact with PP2A to maintain AKT phosphorylation [ 36 ]. These results show that BTBD10 is an important AKT activator, which is an inhibitor of cell death by activating AKT [ 36 , 37 ]. Meanwhile, the results of transcriptome sequencing also showed that almost all the pathways enriched by DEGs were PIK3CB / AKT1- related, this further supports the hypothesis that PI3K/AKT signal is the key pathway for miR-202-5p to regulate the proliferation and apoptosis of goose GCs.…”

Section: Discussionmentioning

confidence: 99%

MiR-202-5p Regulates Geese Follicular Selection by Targeting BTBD10 to Regulate Granulosa Cell Proliferation and Apoptosis

Ran

Xie

et al. 2023

IJMS

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The regulation of granulosa cells (GCs) proliferation and apoptosis is the key step in follicular selection which determines the egg production performance of poultry. miR-202-5p has been reported to be involved in regulating the proliferation and apoptosis of mammalian ovarian GCs. However, its role in regulating the proliferation and apoptosis of goose GCs is still unknown. In the present study, the GCs of pre-hierarchical follicles (phGCs, 8–10 mm) and those of hierarchical follicles (hGCs, F2–F4) were used to investigate the role of miR-202-5p in cell proliferation and apoptosis during follicle selection. In phGCs and hGCs cultured in vitro, miR-202-5p was found to negatively regulate cell proliferation and positively regulate cell apoptosis. The results of RNA-seq showed that BTB Domain Containing 10 (BTBD10) is predicted to be a key target gene for miR-202-5p to regulate the proliferation and apoptosis of GCs. Furthermore, it is confirmed that miR-202-5p can inhibit BTBD10 expression by targeting its 3′UTR region, and BTBD10 was revealed to promote the proliferation and inhibit the apoptosis of phGCs and hGCs. Additionally, co-transfection with BTBD10 effectively prevented miR-202-5p mimic-induced cell apoptosis and the inhibition of cell proliferation. Meanwhile, miR-202-5p also remarkably inhibited the expression of Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB) and AKT Serine/Threonine Kinase 1 (AKT1), while it was significantly restored by BTBD10. Overall, miR-202-5p suppresses the proliferation and promotes the apoptosis of GCs through the downregulation of PIK3CB/AKT1 signaling by targeting BTBD10 during follicular selection. Our study provides a theoretical reference for understanding the molecular mechanism of goose follicular selection, as well as a candidate gene for molecular marker-assisted breeding to improve the geese’ egg production performance.

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BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

Cited by 8 publications

References 39 publications

Single-cell and bulk RNA-seq unveils the immune infiltration landscape associated with cuproptosis in cerebral cavernous malformations

Single-cell and bulk RNA-seq unveils the immune infiltration landscape associated with cuproptosis in cerebral cavernous malformations

Cuproptosis signature and PLCD3 predicts immune infiltration and drug responses in osteosarcoma

MiR-202-5p Regulates Geese Follicular Selection by Targeting BTBD10 to Regulate Granulosa Cell Proliferation and Apoptosis

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