UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR Signaling
Ubiquitin C-terminal hydrolase L5 (UCHL5) is a deubiquitinating enzyme (DUB) that removes ubiquitin from its substrates. Associations between UCHL5 and cancer have been reported in various tissues, but the effect of UCHL5 on bladder cancer has not been thoroughly investigated. This study investigate...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/22/5538 |
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| author | Yuanfei Cao Xin Yan Xiaojie Bai Feng Tang Penghui Si Can Bai Kuerban Tuoheti Linfa Guo Zuhaer Yisha Tao Liu Tongzu Liu |
| author_facet | Yuanfei Cao Xin Yan Xiaojie Bai Feng Tang Penghui Si Can Bai Kuerban Tuoheti Linfa Guo Zuhaer Yisha Tao Liu Tongzu Liu |
| author_sort | Yuanfei Cao |
| collection | DOAJ |
| description | Ubiquitin C-terminal hydrolase L5 (UCHL5) is a deubiquitinating enzyme (DUB) that removes ubiquitin from its substrates. Associations between UCHL5 and cancer have been reported in various tissues, but the effect of UCHL5 on bladder cancer has not been thoroughly investigated. This study investigates the expression and function of UCHL5 in bladder cancer. UCHL5 was shown to be abnormally expressed using IHC of tissue microarray and Western blotting. Several procedures were performed to assess the effect of UCHL5 overexpression or knockdown on bladder cancer, such as cell proliferation, colony formation, wound-healing, and Transwell assays. In addition, RNA-Seq and Western blotting experiments were used to verify the status of downstream signaling pathways. Finally, bladder cancers with knockdown or overexpression of UCHL5 were treated with either SC79 or LY294002 to examine the participation of the AKT/mTOR signaling pathway and the expression of downstream targets c-Myc, SLC25A19, and ICAM5. In contrast to adjacent tissue samples, we discovered that UCHL5 was substantially expressed in bladder cancer samples. We also found that UCHL5 downregulation significantly suppressed both tumor growth in vivo and cell proliferation and migration in vitro. According to RNA-Seq analyses and Western blotting experiments, the expression of c-Myc, SLC25A19, and ICAM5 was modified as a result of UCHL5 activating AKT/mTOR signaling in bladder cancer cells. All things considered, our findings show that increased UCHL5 expression stimulates AKT/mTOR signaling, subsequently triggering the expression of c-Myc, SLC25A19, and ICAM5, which in turn promotes carcinogenesis in bladder cancer. UCHL5 is therefore a potential target for therapy in bladder cancer patients. |
| first_indexed | 2024-03-09T18:26:09Z |
| format | Article |
| id | doaj.art-2d98df217d374d1581876f474e04fc06 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T18:26:09Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2d98df217d374d1581876f474e04fc062023-11-24T07:52:48ZengMDPI AGCancers2072-66942022-11-011422553810.3390/cancers14225538UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR SignalingYuanfei Cao0Xin Yan1Xiaojie Bai2Feng Tang3Penghui Si4Can Bai5Kuerban Tuoheti6Linfa Guo7Zuhaer Yisha8Tao Liu9Tongzu Liu10Department of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaUbiquitin C-terminal hydrolase L5 (UCHL5) is a deubiquitinating enzyme (DUB) that removes ubiquitin from its substrates. Associations between UCHL5 and cancer have been reported in various tissues, but the effect of UCHL5 on bladder cancer has not been thoroughly investigated. This study investigates the expression and function of UCHL5 in bladder cancer. UCHL5 was shown to be abnormally expressed using IHC of tissue microarray and Western blotting. Several procedures were performed to assess the effect of UCHL5 overexpression or knockdown on bladder cancer, such as cell proliferation, colony formation, wound-healing, and Transwell assays. In addition, RNA-Seq and Western blotting experiments were used to verify the status of downstream signaling pathways. Finally, bladder cancers with knockdown or overexpression of UCHL5 were treated with either SC79 or LY294002 to examine the participation of the AKT/mTOR signaling pathway and the expression of downstream targets c-Myc, SLC25A19, and ICAM5. In contrast to adjacent tissue samples, we discovered that UCHL5 was substantially expressed in bladder cancer samples. We also found that UCHL5 downregulation significantly suppressed both tumor growth in vivo and cell proliferation and migration in vitro. According to RNA-Seq analyses and Western blotting experiments, the expression of c-Myc, SLC25A19, and ICAM5 was modified as a result of UCHL5 activating AKT/mTOR signaling in bladder cancer cells. All things considered, our findings show that increased UCHL5 expression stimulates AKT/mTOR signaling, subsequently triggering the expression of c-Myc, SLC25A19, and ICAM5, which in turn promotes carcinogenesis in bladder cancer. UCHL5 is therefore a potential target for therapy in bladder cancer patients.https://www.mdpi.com/2072-6694/14/22/5538UCHL5bladder cancerproliferationmigrationAKTc-Myc |
| spellingShingle | Yuanfei Cao Xin Yan Xiaojie Bai Feng Tang Penghui Si Can Bai Kuerban Tuoheti Linfa Guo Zuhaer Yisha Tao Liu Tongzu Liu UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR Signaling Cancers UCHL5 bladder cancer proliferation migration AKT c-Myc |
| title | UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR Signaling |
| title_full | UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR Signaling |
| title_fullStr | UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR Signaling |
| title_full_unstemmed | UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR Signaling |
| title_short | UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR Signaling |
| title_sort | uchl5 promotes proliferation and migration of bladder cancer cells by activating c myc via akt mtor signaling |
| topic | UCHL5 bladder cancer proliferation migration AKT c-Myc |
| url | https://www.mdpi.com/2072-6694/14/22/5538 |
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