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- Publisher Website: 10.1021/acsnano.3c01199
- Scopus: eid_2-s2.0-85178494856
- PMID: 37966480
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Article: Long Noncoding RNA URB1-Antisense RNA 1 (AS1) Suppresses Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma by Driving Ferritin Phase Separation
Title | Long Noncoding RNA URB1-Antisense RNA 1 (AS1) Suppresses Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma by Driving Ferritin Phase Separation |
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Authors | |
Keywords | ferritin ferroptosis hepatocellular carcinoma sorafenib URB1-AS1 |
Issue Date | 28-Nov-2023 |
Publisher | American Chemical Society |
Citation | ACS Nano, 2023, v. 17, n. 22, p. 22240-22258 How to Cite? |
Abstract | Sorafenib, a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), has been shown to be a potent ferroptosis inducer in HCC. However, we found that there was a lower level of ferroptosis in sorafenib-resistant HCC samples than in sorafenib-sensitive HCC samples, suggesting that sorafenib resistance in HCC may be a result of ferroptosis suppression. Recent reports have shown that long noncoding RNAs (lncRNAs) are involved in programmed cell death (PCD), including apoptosis and ferroptosis. This study aimed to investigate the roles and underlying molecular mechanisms of lncRNAs in sorafenib-induced ferroptosis in HCC cells. Using lncRNA sequencing, we identified a ferroptosis-related lncRNA, URB1-antisense RNA 1 (AS1), which was highly expressed in sorafenib-resistant HCC samples and predicted poor survival in HCC. Furthermore, URB1-AS1 mitigates sorafenib-induced ferroptosis by inducing ferritin phase separation and reducing the cellular free iron content. Hypoxia inducible factor (HIF)-1α was identified as a key factor promoting URB1-AS1 expression in sorafenib-resistant HCC cells. Notably, we found that specifically inhibiting the expression of URB1-AS1 with N-acetylgalactosamine (GalNAc)-small interfering (si)URB1-AS1 successfully enhanced the sensitivity of HCC cells to sorafenib in an in vivo tumor model. Our study uncovered a critical role for URB1-AS1 in the repression of ferroptosis, suggesting URB1-AS1 targeting may represent a potential approach to overcome sorafenib resistance in HCC. |
Persistent Identifier | http://hdl.handle.net/10722/344352 |
ISSN | 2023 Impact Factor: 15.8 2023 SCImago Journal Rankings: 4.593 |
DC Field | Value | Language |
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dc.contributor.author | Gao, Yuan | - |
dc.contributor.author | Tong, Man | - |
dc.contributor.author | Wong, Tin Lok | - |
dc.contributor.author | Ng, Kai Yu | - |
dc.contributor.author | Xie, Yu Nong | - |
dc.contributor.author | Wang, Zhaowei | - |
dc.contributor.author | Yu, Huajian | - |
dc.contributor.author | Loh, Jia Jian | - |
dc.contributor.author | Li, Meng | - |
dc.contributor.author | Ma, Stephanie | - |
dc.date.accessioned | 2024-07-24T13:50:56Z | - |
dc.date.available | 2024-07-24T13:50:56Z | - |
dc.date.issued | 2023-11-28 | - |
dc.identifier.citation | ACS Nano, 2023, v. 17, n. 22, p. 22240-22258 | - |
dc.identifier.issn | 1936-0851 | - |
dc.identifier.uri | http://hdl.handle.net/10722/344352 | - |
dc.description.abstract | Sorafenib, a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), has been shown to be a potent ferroptosis inducer in HCC. However, we found that there was a lower level of ferroptosis in sorafenib-resistant HCC samples than in sorafenib-sensitive HCC samples, suggesting that sorafenib resistance in HCC may be a result of ferroptosis suppression. Recent reports have shown that long noncoding RNAs (lncRNAs) are involved in programmed cell death (PCD), including apoptosis and ferroptosis. This study aimed to investigate the roles and underlying molecular mechanisms of lncRNAs in sorafenib-induced ferroptosis in HCC cells. Using lncRNA sequencing, we identified a ferroptosis-related lncRNA, URB1-antisense RNA 1 (AS1), which was highly expressed in sorafenib-resistant HCC samples and predicted poor survival in HCC. Furthermore, URB1-AS1 mitigates sorafenib-induced ferroptosis by inducing ferritin phase separation and reducing the cellular free iron content. Hypoxia inducible factor (HIF)-1α was identified as a key factor promoting URB1-AS1 expression in sorafenib-resistant HCC cells. Notably, we found that specifically inhibiting the expression of URB1-AS1 with N-acetylgalactosamine (GalNAc)-small interfering (si)URB1-AS1 successfully enhanced the sensitivity of HCC cells to sorafenib in an in vivo tumor model. Our study uncovered a critical role for URB1-AS1 in the repression of ferroptosis, suggesting URB1-AS1 targeting may represent a potential approach to overcome sorafenib resistance in HCC. | - |
dc.language | eng | - |
dc.publisher | American Chemical Society | - |
dc.relation.ispartof | ACS Nano | - |
dc.subject | ferritin | - |
dc.subject | ferroptosis | - |
dc.subject | hepatocellular carcinoma | - |
dc.subject | sorafenib | - |
dc.subject | URB1-AS1 | - |
dc.title | Long Noncoding RNA URB1-Antisense RNA 1 (AS1) Suppresses Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma by Driving Ferritin Phase Separation | - |
dc.type | Article | - |
dc.identifier.doi | 10.1021/acsnano.3c01199 | - |
dc.identifier.pmid | 37966480 | - |
dc.identifier.scopus | eid_2-s2.0-85178494856 | - |
dc.identifier.volume | 17 | - |
dc.identifier.issue | 22 | - |
dc.identifier.spage | 22240 | - |
dc.identifier.epage | 22258 | - |
dc.identifier.eissn | 1936-086X | - |
dc.identifier.issnl | 1936-0851 | - |