MYBL2 accelerates epithelial-mesenchymal transition and hepatoblastoma metastasis via the Smad/SNAI1 pathway.
Am J Cancer Res
; 12(5): 1960-1981, 2022.
Article
in En
| MEDLINE
| ID: mdl-35693071
ABSTRACT
Hepatoblastoma (HB) accounts for the majority of hepatic malignancies in children. Although the prognosis of patients with HB has improved in past decades, metastasis is an indicator of poor overall survival. Herein, we applied single-cell RNA sequencing to explore the transcriptomic profiling of 25,264 metastatic cells isolated from the lungs of two patients with HB. The transcriptomes uncovered the heterogeneity of malignant cells after metastatic lung colonization, and these cells had varied expression signatures associated with the cell cycle, epithelial-mesenchymal plasticity, and hepatic differentiation. Single-cell regulatory network inference and clustering (SCENIC) was utilized to identify the co-expressed transcriptional factors which regulated and represented the different cell states. We further screened the key factor by bioinformatics analysis and found that MYBL2 upregulation was significantly associated with metastasis and poor prognosis. The relationship between ectopic MYBL2 and metastasis was subsequently proved by immunohistochemistry (IHC) of HB tissues, and the functions of MYBL2 in promoting proliferation, migration, and epithelial-to-mesenchymal transition (EMT) were verified by in vitro and in vivo assays. Importantly, the levels of Smad2/3 phosphorylation and SNAI1 expression were increased in MYBL2-transfected cells. Consequently, these results indicated that the MYBL2-controlled Smad/SNAI1 pathway induced EMT and promoted HB tumorigenesis and metastasis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
Am J Cancer Res
Year:
2022
Document type:
Article
Affiliation country:
China
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA