Circ<i>MTA2</i> Drives Gastric Cancer Progression through Suppressing <i>MTA2</i> Degradation via Interacting with UCHL3
Our previous study has reported that metastasis-associated protein 2 (<i>MTA2</i>) plays essential roles in tumorigenesis and aggressiveness of gastric cancer (GC). However, the underlying molecular mechanisms of <i>MTA2</i>-mediated GC and its upstream regulation mechanism r...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/5/2817 |
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| author | Gengchen Xie Bo Lei Zhijie Yin Fei Xu Xinghua Liu |
| author_facet | Gengchen Xie Bo Lei Zhijie Yin Fei Xu Xinghua Liu |
| author_sort | Gengchen Xie |
| collection | DOAJ |
| description | Our previous study has reported that metastasis-associated protein 2 (<i>MTA2</i>) plays essential roles in tumorigenesis and aggressiveness of gastric cancer (GC). However, the underlying molecular mechanisms of <i>MTA2</i>-mediated GC and its upstream regulation mechanism remain elusive. In this study, we identified a novel circular RNA (circRNA) generated from the <i>MTA2</i> gene (circ<i>MTA2</i>) as a crucial regulator in GC progression. Circ<i>MTA2</i> was highly expressed in GC tissues and cell lines, and circ<i>MTA2</i> promoted the proliferation, invasion, and metastasis of GC cells both in vitro and in vivo. Mechanistically, circ<i>MTA2</i> interacted with ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) to restrain <i>MTA2</i> ubiquitination and stabilize <i>MTA2</i> protein expression, thereby facilitating tumor progression. Moreover, circ<i>MTA2</i> was mainly encapsulated and transported by exosomes to promote GC cell progression. Taken together, these findings uncover that circ<i>MTA2</i> suppresses <i>MTA2</i> degradation by interacting with UCHL3, thereby promoting GC progression. In conclusion, we identified a cancer-promoting axis (circ<i>MTA2</i>/UCHL3/<i>MTA2</i>) in GC progression, which paves the way for us to design and synthesize targeted inhibitors as well as combination therapies. |
| first_indexed | 2024-04-25T00:27:47Z |
| format | Article |
| id | doaj.art-7c2447237b7f44f68feb4cdd7cf28b31 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:27:47Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7c2447237b7f44f68feb4cdd7cf28b312024-03-12T16:46:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01255281710.3390/ijms25052817Circ<i>MTA2</i> Drives Gastric Cancer Progression through Suppressing <i>MTA2</i> Degradation via Interacting with UCHL3Gengchen Xie0Bo Lei1Zhijie Yin2Fei Xu3Xinghua Liu4Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaOur previous study has reported that metastasis-associated protein 2 (<i>MTA2</i>) plays essential roles in tumorigenesis and aggressiveness of gastric cancer (GC). However, the underlying molecular mechanisms of <i>MTA2</i>-mediated GC and its upstream regulation mechanism remain elusive. In this study, we identified a novel circular RNA (circRNA) generated from the <i>MTA2</i> gene (circ<i>MTA2</i>) as a crucial regulator in GC progression. Circ<i>MTA2</i> was highly expressed in GC tissues and cell lines, and circ<i>MTA2</i> promoted the proliferation, invasion, and metastasis of GC cells both in vitro and in vivo. Mechanistically, circ<i>MTA2</i> interacted with ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) to restrain <i>MTA2</i> ubiquitination and stabilize <i>MTA2</i> protein expression, thereby facilitating tumor progression. Moreover, circ<i>MTA2</i> was mainly encapsulated and transported by exosomes to promote GC cell progression. Taken together, these findings uncover that circ<i>MTA2</i> suppresses <i>MTA2</i> degradation by interacting with UCHL3, thereby promoting GC progression. In conclusion, we identified a cancer-promoting axis (circ<i>MTA2</i>/UCHL3/<i>MTA2</i>) in GC progression, which paves the way for us to design and synthesize targeted inhibitors as well as combination therapies.https://www.mdpi.com/1422-0067/25/5/2817CircRNAs<i>MTA2</i>gastric cancerUCHL3ubiquitination |
| spellingShingle | Gengchen Xie Bo Lei Zhijie Yin Fei Xu Xinghua Liu Circ<i>MTA2</i> Drives Gastric Cancer Progression through Suppressing <i>MTA2</i> Degradation via Interacting with UCHL3 International Journal of Molecular Sciences CircRNAs <i>MTA2</i> gastric cancer UCHL3 ubiquitination |
| title | Circ<i>MTA2</i> Drives Gastric Cancer Progression through Suppressing <i>MTA2</i> Degradation via Interacting with UCHL3 |
| title_full | Circ<i>MTA2</i> Drives Gastric Cancer Progression through Suppressing <i>MTA2</i> Degradation via Interacting with UCHL3 |
| title_fullStr | Circ<i>MTA2</i> Drives Gastric Cancer Progression through Suppressing <i>MTA2</i> Degradation via Interacting with UCHL3 |
| title_full_unstemmed | Circ<i>MTA2</i> Drives Gastric Cancer Progression through Suppressing <i>MTA2</i> Degradation via Interacting with UCHL3 |
| title_short | Circ<i>MTA2</i> Drives Gastric Cancer Progression through Suppressing <i>MTA2</i> Degradation via Interacting with UCHL3 |
| title_sort | circ i mta2 i drives gastric cancer progression through suppressing i mta2 i degradation via interacting with uchl3 |
| topic | CircRNAs <i>MTA2</i> gastric cancer UCHL3 ubiquitination |
| url | https://www.mdpi.com/1422-0067/25/5/2817 |
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