Focal adhesion kinase and its epigenetic interactors as diagnostic and therapeutic hints for pediatric hepatoblastoma DOI Creative Commons
Maria Rita Braghini, Cristiano De Stefanis, Francesca Tiano

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 14, 2024

Background Hepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite progress in HB treatment, investigating pathomechanisms to optimize stratification and therapies remains a focal point improve outcome for high-risk patients. Methods Here, we pointed explore impact of these mechanisms HB. An observational study was performed on liver samples from cohort 17 patients with diagnosis two normal samples. The vitro experiments were executed Huh6 human cell line treated FAK inhibitor TAE226. Results Our results highlight significant up-regulation mRNA protein expression livers respect livers. increased total Tyr397 phosphorylated (pTyr397FAK) significantly correlated some epigenetic regulators histone H3 methylation acetylation. Of note, pTyr397FAK, N-methyltransferase enzyme (EZH2) tri-methylation H3K27 residue tumor size alpha-fetoprotein (AFP) levels. Finally, TAE226 caused reduction regulators, AFP , EPCAM OCT4 SOX2 association anti-proliferative pro-apoptotic effects cells. Conclusion suggest role that requires further investigations mainly focused exploration its effective diagnostic therapeutic translatability.

Language: Английский

RAB6A functions as a critical modulator of the stem‐like subsets in cholangiocarcinoma DOI

Liangfang Yang,

Zhiwen Zhu, Yang Zheng

et al.

Molecular Carcinogenesis, Journal Year: 2023, Volume and Issue: 62(10), P. 1460 - 1473

Published: June 6, 2023

Abstract RAB6A is a member of RAB GTPase family and plays an important role in the targeted transport neurotrophic receptors inflammatory cytokines. RAB6A‐mediated secretory pathway involved many physiological pathological processes. Defects may lead to development diseases, including cancer. However, its cholangiocarcinoma (CCA) has not yet been revealed. We explored regulatory stem‐like subsets CCA. showed that knockdown (KD) impedes cancer stem cells (CSCs) properties epithelial−mesenchymal transition vitro suppression inhibits tumor growth vivo. screened target cargos CCA identified extracellular matrix component as cargo. binds directly OPN, KD suppressed OPN secretion inhibited interaction between αV integrin receptor. Moreover, AKT signaling pathway, which downstream effector receptor signaling. In addition, shRNA targeting blocked endogenous expression consequently weakened CSCs RAB6A‐formed spheres. Similarly, inhibitor signaling, MK2206 also oncogenic function cells. conclusion, our findings sustains phenotype maintenance by modulating consequentially activating pathway. Targeting RAB6A/OPN axis be effective strategy for therapy.

Language: Английский

Citations

3

Identification of immune-related genes and patient selection for hepatocellular carcinoma immunotherapy DOI Open Access
Zhendong Chen, Jia‐Yuan Luo, Yuping Ye

et al.

Translational Cancer Research, Journal Year: 2023, Volume and Issue: 12(5), P. 1210 - 1231

Published: April 14, 2023

Background: Hepatocellular carcinoma (HCC) is a malignant disease with poor prognosis.Among the treatment strategies for HCC, tumor immunotherapy (TIT) promising research hotspot, in which identifying novel immune-related biomarkers and selecting suitable patient population are urgent issues to be solved.Methods: In this study, an abnormal expression map of HCC cell genes was constructed using public high-throughput data from 7,384 samples (3,941 vs. 3,.Through singlecell RNA sequencing (scRNA-seq) trajectory analysis, defined as potential drivers differentiation development were selected.By screening both those associated high development, series target identified.Coexpression analysis performed Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) find specific candidate involved similar biological processes.Subsequently, nonnegative matrix factorization (NMF) conducted select patients based on coexpression network genes.Results: HSP90AA1, CDK4, HSPA8, HSPH1, HSPA5 identified prognosis prediction HCC.Through use our molecular classification system, function module containing 5 genes, characteristics found candidates TIT.Conclusions: These findings provide new insights into selection populations future immunotherapy.

Language: Английский

Citations

2

Development and Optimization of a Prognostic Model Associated with Stemness Genes in Hepatocellular Carcinoma DOI Creative Commons

Kefen Zhang,

Kaisheng Xie,

Xin Huo

et al.

BioMed Research International, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 28

Published: Oct. 5, 2022

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, which associated with a variety risk factors. Cancer stem cells are self-renewal cells, can promote occurrence and metastasis tumors enhance drug resistance tumor treatment. This study aimed to develop stemness score model assess prognosis hepatocellular patients for optimization The single-cell sequencing data GSE149614 was downloaded from GEO database. Then, we compared gene expression hepatic other hepatocytes in samples screen differentially expressed genes related stemness. R package “clusterProfiler” used explore potential function stemness-related genes. We then constructed prognostic using LASSO regression analysis based on TCGA GSE14520 cohorts. associations clinical features, sensitivity, mutation, immune microenvironment were further explored. “rms” construct nomogram model. A total 18 enrolled Kaplan-Meier proved good performance at predicting overall survival (OS) HCC patients. closely HCC. infiltration level CD8+ T lower, tumor-associated macrophages higher high-stemness score, indicating an immunosuppressive microenvironment. Our established that reliably predicts OS findings may help clarify biological characteristics progression future diagnosis therapy

Language: Английский

Citations

3

Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality DOI Creative Commons

Qianqian Guo,

Hai Qin,

Zelong Chen

et al.

Genes & Diseases, Journal Year: 2024, Volume and Issue: 12(3), P. 101311 - 101311

Published: April 17, 2024

The ubiquitin (Ub) system, a ubiquitous presence across eukaryotes, plays crucial role in the precise orchestration of diverse cellular protein processes. From steering signaling pathways and orchestrating cell cycle progression to guiding receptor trafficking modulating immune responses, this process regulating various biological functions. dysregulation Ub-mediated prevalent cancers ushers spectrum clinical outcomes ranging from tumorigenesis metastasis recurrence drug resistance. Ubiquitination, linchpin mediated by Ub, assumes central mantle molding dynamics. It navigates transitions cues ultimately shapes destiny proteins. Recent years have witnessed an upsurge momentum surrounding development protein-based therapeutics aimed at targeting Ub system under sway cancer stem cells. article provides comprehensive overview ongoing in-depth discussions regarding regulation its impact on Amidst tapestry insights, delves into expansive roles E3 ligases, deubiquitinases, transcription factors entwined with Furthermore, spotlight turns interplay pivotal Notch, Hedgehog, Wnt/β-catenin, Hippo-YAP all play cells followed specific modulation Ub-proteasome.

Language: Английский

Citations

0

Focal adhesion kinase and its epigenetic interactors as diagnostic and therapeutic hints for pediatric hepatoblastoma DOI Creative Commons
Maria Rita Braghini, Cristiano De Stefanis, Francesca Tiano

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 14, 2024

Background Hepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite progress in HB treatment, investigating pathomechanisms to optimize stratification and therapies remains a focal point improve outcome for high-risk patients. Methods Here, we pointed explore impact of these mechanisms HB. An observational study was performed on liver samples from cohort 17 patients with diagnosis two normal samples. The vitro experiments were executed Huh6 human cell line treated FAK inhibitor TAE226. Results Our results highlight significant up-regulation mRNA protein expression livers respect livers. increased total Tyr397 phosphorylated (pTyr397FAK) significantly correlated some epigenetic regulators histone H3 methylation acetylation. Of note, pTyr397FAK, N-methyltransferase enzyme (EZH2) tri-methylation H3K27 residue tumor size alpha-fetoprotein (AFP) levels. Finally, TAE226 caused reduction regulators, AFP , EPCAM OCT4 SOX2 association anti-proliferative pro-apoptotic effects cells. Conclusion suggest role that requires further investigations mainly focused exploration its effective diagnostic therapeutic translatability.

Language: Английский

Citations

0