HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH..
YTH domain family 2 (YTHDF2) is the first identified N6-methyladenosine (m6 A) reader that regulates the status of mRNA. It has been reported that overexpressed YTHDF2 promotes carcinogenesis; yet, its role in hepatocellular carcinoma (HCC) is elusive. Herein, it is demonstrated that YTHDF2 is upregulated and can predict poor outcomes in HCC. Decreased ubiquitination levels of YTHDF2 contribute to the upregulation of YTHDF2. Furthermore, heat shock protein 90 beta (HSP90β) and STIP1 homology and U-box-containing protein 1 (STUB1) physically interact with YTHDF2 in the cytoplasm. Mechanically, the large and small middle domain of HSP90β is required for its interaction with STUB1 and YTHDF2. HSP90β inhibits the STUB1-induced degradation of YTHDF2 to elevate the expression of YTHDF2 and to further boost the proliferation and sorafenib resistance of HCC. Moreover, HSP90β and YTHDF2 are upregulated, while STUB1 is downregulated in HCC tissues. The expression of HSP90β is positively correlated with the YTHDF2 protein level, whereas the expression of STUB1 is negatively correlated with the protein levels of YTHDF2 and HSP90β. These findings deepen the understanding of how YTHDF2 is regulated to drive HCC progression and provide potential targets for treating HCC.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 10(2023), 27 vom: 01. Sept., Seite e2302025 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liao, Yuning [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.10.2023 Date Revised 11.10.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/advs.202302025 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM360152481 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM360152481 | ||
| 003 | DE-627 | ||
| 005 | 20231226082413.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/advs.202302025 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1200.xml |
| 035 | |a (DE-627)NLM360152481 | ||
| 035 | |a (NLM)37515378 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liao, Yuning |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.10.2023 | ||
| 500 | |a Date Revised 11.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH. | ||
| 520 | |a YTH domain family 2 (YTHDF2) is the first identified N6-methyladenosine (m6 A) reader that regulates the status of mRNA. It has been reported that overexpressed YTHDF2 promotes carcinogenesis; yet, its role in hepatocellular carcinoma (HCC) is elusive. Herein, it is demonstrated that YTHDF2 is upregulated and can predict poor outcomes in HCC. Decreased ubiquitination levels of YTHDF2 contribute to the upregulation of YTHDF2. Furthermore, heat shock protein 90 beta (HSP90β) and STIP1 homology and U-box-containing protein 1 (STUB1) physically interact with YTHDF2 in the cytoplasm. Mechanically, the large and small middle domain of HSP90β is required for its interaction with STUB1 and YTHDF2. HSP90β inhibits the STUB1-induced degradation of YTHDF2 to elevate the expression of YTHDF2 and to further boost the proliferation and sorafenib resistance of HCC. Moreover, HSP90β and YTHDF2 are upregulated, while STUB1 is downregulated in HCC tissues. The expression of HSP90β is positively correlated with the YTHDF2 protein level, whereas the expression of STUB1 is negatively correlated with the protein levels of YTHDF2 and HSP90β. These findings deepen the understanding of how YTHDF2 is regulated to drive HCC progression and provide potential targets for treating HCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HSP90β | |
| 650 | 4 | |a STUB1 | |
| 650 | 4 | |a YTHDF2 | |
| 650 | 4 | |a hepatocellular carcinoma | |
| 650 | 4 | |a ubiquitination | |
| 650 | 7 | |a RNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Sorafenib |2 NLM | |
| 650 | 7 | |a 9ZOQ3TZI87 |2 NLM | |
| 650 | 7 | |a STUB1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a Ubiquitin-Protein Ligases |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a YTHDF2 protein, human |2 NLM | |
| 650 | 7 | |a HSP90 Heat-Shock Proteins |2 NLM | |
| 700 | 1 | |a Liu, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Cuifu |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Qiucheng |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Weiyao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Yuanhui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Xuefen |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Wenshuang |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Shusha |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Gengxi |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Hongbiao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Advanced science (Weinheim, Baden-Wurttemberg, Germany) |d 2014 |g 10(2023), 27 vom: 01. Sept., Seite e2302025 |w (DE-627)NLM252851455 |x 2198-3844 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2023 |g number:27 |g day:01 |g month:09 |g pages:e2302025 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/advs.202302025 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2023 |e 27 |b 01 |c 09 |h e2302025 | ||