| Literature DB >> 33750796 |
Xia Wang1,2,3, Jin Wang4, Yu-Man Tsui2,3, Chaoran Shi1,2, Ying Wang1,2,5, Xin Zhang2,3, Qian Yan1,2, Miao Chen1,2, Chen Jiang1,6,7, Yun-Fei Yuan6, Chun-Ming Wong2,3, Ming Liu1,2,8, Zeng-Yu Feng9, Honglin Chen10, Irene Oi Lin Ng2,3, Lingxi Jiang11,12, Xin-Yuan Guan13,14.
Abstract
Growing evidences suggest that cancer stem cells exhibit many molecular characteristics and phenotypes similar to their ancestral progenitor cells. In the present study, human embryonic stem cells are induced to differentiate into hepatocytes along hepatic lineages to mimic liver development in vitro. A liver progenitor specific gene, RALY RNA binding protein like (RALYL), is identified. RALYL expression is associated with poor prognosis, poor differentiation, and metastasis in clinical HCC patients. Functional studies reveal that RALYL could promote HCC tumorigenicity, self-renewal, chemoresistance, and metastasis. Moreover, molecular mechanism studies show that RALYL could upregulate TGF-β2 mRNA stability by decreasing N6-methyladenosine (m6A) modification. TGF-β signaling and the subsequent PI3K/AKT and STAT3 pathways, upregulated by RALYL, contribute to the enhancement of HCC stemness. Collectively, RALYL is a liver progenitor specific gene and regulates HCC stemness by sustaining TGF-β2 mRNA stability. These findings may inspire precise therapeutic strategies for HCC.Entities:
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Year: 2021 PMID： 33750796 PMCID： PMC7943813 DOI： 10.1038/s41467-021-21828-7
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919