Molecular Mechanisms of Hepatoblastoma

Zhang, Yi; Solinas, A; Cairo, Stefano; Evert, Matthias; Chen, Xin; Calvisi, Diego F.

doi:10.1055/s-0040-1722645

Cited by 25 publications

(32 citation statements)

References 148 publications

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“…The most recurrent mutation is found in the CTNNB1 gene, the key effector of the Wnt/β -catenin signaling pathway, mainly harboring exon 3 mutations or deletions [11,12] . Besides CTNNB1, additional mutations in other genes have been reported in different studies [Table 1] [4,12,[14][15][16][17][18][19][20] .…”

Section: Molecular Mechanisms Of Carcinogenesis In Hbmentioning

confidence: 99%

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Epigenetics in hepatoblastoma

Clavería-Cabello¹,

Arechederra²,

Berasain³

et al. 2021

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Hepatoblastoma (HB) is the most frequent pediatric primary liver tumor. When the tumoral lesions can be resected, prognosis is generally favorable. However, there is a significant number of cases in which resection is not possible at diagnosis, and patients usually receive neo-adjuvant cisplatin-based chemotherapy prior to surgery. Unfortunately, some HBs develop resistance to initial chemotherapy or after recurrence, progressing to metastatic disease. Moreover, long-term side effects of chemotherapy remain a serious concern. Understanding the molecular bases of HB development and progression is thus essential for the identification of more efficacious therapies. HBs have a very low mutational burden, and the most frequent mutations occur in the CTNN1B gene (> 80% of cases) and to a lesser extent in NFE2L2 (~10% of cases). These observations suggest that other pathogenic processes besides genetic mutations may play a role in HB tumorigenesis. Epigenetic mechanisms encompass a variety of molecular processes with a tremendous potential to regulate gene expression. They include the covalent modifications of DNA and histones, the activity of enzymatic chromatin remodelers, and the expression of noncoding RNAs. Dysregulation of epigenetic processes has clearly become a hallmark of cancer. Regarding HB, recent studies have explored its epigenetic landscape, the expression of specific epigenetic effectors, and the tumorigenic consequences of epigenetic alterations. The reversible nature of most epigenetic modifications and the possibility to target non-coding RNAs may pave the way for new therapeutic avenues in HB. Here, we summarize and discuss the most relevant findings in this less explored aspect of HB.

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Section: Molecular Mechanisms Of Carcinogenesis In Hbmentioning

confidence: 99%

“…1%-7% [14,15] APC 7%-14% [14,19,20] ARID1A 2.9%-3.1% [16,17] NFE2L2/KEAP1, HGF/c-Met, PI3K/AKT/mTOR, SP/NK-1R, and IGF pathways. The role of these pathways in the development and progression of HB was recently reviewed by Zhang et al [21] .…”

Section: Axin1mentioning

confidence: 99%

Epigenetics in hepatoblastoma

Clavería-Cabello¹,

Arechederra²,

Berasain³

et al. 2021

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Section: Lncrnas and Circrnas In Cancersmentioning

confidence: 99%

“…170 The embryonic subtype is the most common variant of hepatoblastoma, and its cells feature prominent hyperbasophilic nuclei and small cytoplasm, such as those found in the liver during the first weeks of pregnancy. 171 LncRNA zinc finger antisense 1 (ZFAS1), as an oncogene, was highly regulated in hepatoblastoma, which is associated with poor overall survival and an aggressive phenotype. Moreover, overexpressing ZFAS1 can activate the expression of HGF/c-Met signaling-associated molecules, while silencing ZFAS1 has the opposite effect.…”

Section: Hepatoblastomamentioning

confidence: 99%

LncRNAs and CircRNAs in cancer

Yin

Lin

et al. 2022

MedComm

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It is well known that noncoding RNAs (ncRNAs) cannot encode proteins, but they can play important regulatory roles in tumors by combining with proteins, RNAs, and DNAs. As more and more studies reveal the important roles and underlying mechanisms of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in cancer, their huge application potential in cancer therapy cannot be ignored. For example, lncRNAs can be involved in tumor‐related signal transduction pathways, cell cycle control, DNA damage, epigenetic regulation, and microRNA control. A group of studies confirmed that abnormal expression of lncRNAs can affect cancer progression. Furthermore, as covalently closed continuous circular ncRNAs, many recent studies have shown that circRNAs have regulatory effects and other important biological significances in cancer. Interestingly, circRNAs were found to have translational functions. This has greatly attracted people's attention to circRNAs research. In this review, we introduce the important roles of lncRNAs and circRNAs in some representative cancers, respectively. Furthermore, we focus on the biological functions and important clinical therapeutic implications of lnRNAs and circRNAs in neuroblastoma. Our review also focuses on providing rationale and relevant references for novel biomarkers for neuroblastoma diagnosis, prognosis, and treatment.

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“…At present, surgery is the major treatment for hepatoblastoma. However, the effect remains not ideal [10,11]. Therefore, timely treatment of hepatoblastoma is of great significance for controlling this malignancy.…”

Section: Introductionmentioning

confidence: 99%

miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells

Zai

Jiang

et al. 2021

Journal of Immunology Research

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Background. Extracellular vesicles (EVs) can deliver miRNAs between cells and play a crucial role in hepatoblastoma progression. In this study, we explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Methods. Bioinformatics analysis was performed to explore the differentially expressed miRNAs between the hepatoblastoma and adjacent normal tissues. TEM, NTA, and western blotting were conducted to identify EVs. The expression of miR-126-3p, miR-126-5p, miR-30b-3p, miR-30b-3p, SRY, IL-1α, IL-6, and TGF-β was detected by RT-qPCR. Immunofluorescence (IF) was used to analyze the expression of PKH67, and flow cytometry was applied to assess the ratio of CD44+ CD90+ CD133+ cells. ELISA was used to evaluate the levels of IL-6 and TGF-β. A xenograft mouse model was constructed to detect the function of EVs with downregulated miR-126. IHC was performed to calculate β-catenin levels in tumor tissues. Results. miR-126 was upregulated in hepatoblastoma. EVs derived from hepatoblastoma cells significantly increased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, and TGF-β in bone marrow mesenchymal stem cells (BMSCs), while EVs with downregulated miR-126 reversed these phenomena. miR-126 downregulation notably attenuated hepatoblastoma tumor growth and decreased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, TGF-β, and β-catenin in tumor tissues of mice. Furthermore, EVs with downregulated miR-126 inhibited the differentiation of BMSCs into cancer stem cells. Conclusions. Exosomal miR-126 derived from hepatoblastoma cells promoted the tumorigenesis of liver cancer through inducing the differentiation of BMSCs into cancer stem cells.

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Molecular Mechanisms of Hepatoblastoma

Cited by 25 publications

References 148 publications

Epigenetics in hepatoblastoma

Epigenetics in hepatoblastoma

LncRNAs and CircRNAs in cancer

miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells

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