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- Publisher Website: 10.1038/s41467-021-21828-7
- Scopus: eid_2-s2.0-85102251421
- PMID: 33750796
- WOS: WOS:000627829600004
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Article: RALYL increases hepatocellular carcinoma stemness by sustaining the mRNA stability of TGF-β2
Title | RALYL increases hepatocellular carcinoma stemness by sustaining the mRNA stability of TGF-β2 |
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Authors | |
Issue Date | 2021 |
Publisher | Nature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html |
Citation | Nature Communications, 2021, v. 12 n. 1, p. article no. 1518 How to Cite? |
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. |
Persistent Identifier | http://hdl.handle.net/10722/299289 |
ISSN | 2023 Impact Factor: 14.7 2023 SCImago Journal Rankings: 4.887 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Wang, X | - |
dc.contributor.author | Wang, J | - |
dc.contributor.author | Tsui, YM | - |
dc.contributor.author | Shi, C | - |
dc.contributor.author | Wang, Y | - |
dc.contributor.author | Zhang, X | - |
dc.contributor.author | Yan, Q | - |
dc.contributor.author | Chen, M | - |
dc.contributor.author | Jiang, C | - |
dc.contributor.author | Yuan, YF | - |
dc.contributor.author | Wong, CM | - |
dc.contributor.author | Liu, M | - |
dc.contributor.author | Feng, ZY | - |
dc.contributor.author | Chen, H | - |
dc.contributor.author | Ng, IOL | - |
dc.contributor.author | Jiang, L | - |
dc.contributor.author | Guan, XY | - |
dc.date.accessioned | 2021-05-10T06:59:41Z | - |
dc.date.available | 2021-05-10T06:59:41Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Nature Communications, 2021, v. 12 n. 1, p. article no. 1518 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/10722/299289 | - |
dc.description.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. | - |
dc.language | eng | - |
dc.publisher | Nature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html | - |
dc.relation.ispartof | Nature Communications | - |
dc.rights | Nature Communications. Copyright © Nature Research: Fully open access journals. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | RALYL increases hepatocellular carcinoma stemness by sustaining the mRNA stability of TGF-β2 | - |
dc.type | Article | - |
dc.identifier.email | Wang, X: wxia0951@hku.hk | - |
dc.identifier.email | Wang, J: wangjink@hku.hk | - |
dc.identifier.email | Tsui, YM: ymtsui@hku.hk | - |
dc.identifier.email | Zhang, X: vanilla6@hku.hk | - |
dc.identifier.email | Chen, M: miaoc@hku.hk | - |
dc.identifier.email | Wong, CM: jcmwong@hku.hk | - |
dc.identifier.email | Ng, IOL: iolng@hku.hk | - |
dc.identifier.email | Guan, XY: xyguan@hku.hk | - |
dc.identifier.authority | Wong, CM=rp00231 | - |
dc.identifier.authority | Ng, IOL=rp00335 | - |
dc.identifier.authority | Guan, XY=rp00454 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41467-021-21828-7 | - |
dc.identifier.pmid | 33750796 | - |
dc.identifier.pmcid | PMC7943813 | - |
dc.identifier.scopus | eid_2-s2.0-85102251421 | - |
dc.identifier.hkuros | 322379 | - |
dc.identifier.volume | 12 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | article no. 1518 | - |
dc.identifier.epage | article no. 1518 | - |
dc.identifier.isi | WOS:000627829600004 | - |
dc.publisher.place | United Kingdom | - |