Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2
Testicular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important...
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| Format: | Article |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.670409/full |
| _version_ | 1818908310352429056 |
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| author | Huan Wang Wenqin Luo Xuliang Wang Dingwei Xue Liangliang Ren Li Xu Guangju Ge Liqun Xia Shicheng Yu Mingchao Wang Zhenwei Zhou Gonghui Li Haiyang Wu |
| author_facet | Huan Wang Wenqin Luo Xuliang Wang Dingwei Xue Liangliang Ren Li Xu Guangju Ge Liqun Xia Shicheng Yu Mingchao Wang Zhenwei Zhou Gonghui Li Haiyang Wu |
| author_sort | Huan Wang |
| collection | DOAJ |
| description | Testicular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important role in prostate cancer, renal cell carcinoma, and hepatocellular carcinoma; however, its potential link to bladder cancer (BC) remains unknown. This study found that bladder cancer exhibited a higher expression of TR4 compared to normal tissues. Overexpressed TR4 promoted the bladder cancer cell proliferation, and knocked down TR4 with TR4-siRNA suppressed the bladder cancer cell proliferation. Mechanistic studies reveal that TR4 functions by altering the expression of Bcl-2 to regulate apoptosis in bladder cancer cells. Furthermore, knocking down Bcl-2 reversed the BC proliferation induced by TR4. In vivo, we also confirmed that TR4 knockdown mice (TR4+/−) showed slower bladder cancer growth than wild-type mice (TR4+/+) induced by the carcinogenic chemicals. Moreover, TR4+/− mice showed a lower grade of histopathology than the control group. In conclusion, these results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment. |
| first_indexed | 2024-12-19T22:08:59Z |
| format | Article |
| id | doaj.art-e620785111d243719cc834b79a80d229 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-19T22:08:59Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-e620785111d243719cc834b79a80d2292022-12-21T20:03:59ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-09-01810.3389/fmolb.2021.670409670409Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2Huan Wang0Wenqin Luo1Xuliang Wang2Dingwei Xue3Liangliang Ren4Li Xu5Guangju Ge6Liqun Xia7Shicheng Yu8Mingchao Wang9Zhenwei Zhou10Gonghui Li11Haiyang Wu12Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, The Affiliated Hangzhou First People’s Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaTesticular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important role in prostate cancer, renal cell carcinoma, and hepatocellular carcinoma; however, its potential link to bladder cancer (BC) remains unknown. This study found that bladder cancer exhibited a higher expression of TR4 compared to normal tissues. Overexpressed TR4 promoted the bladder cancer cell proliferation, and knocked down TR4 with TR4-siRNA suppressed the bladder cancer cell proliferation. Mechanistic studies reveal that TR4 functions by altering the expression of Bcl-2 to regulate apoptosis in bladder cancer cells. Furthermore, knocking down Bcl-2 reversed the BC proliferation induced by TR4. In vivo, we also confirmed that TR4 knockdown mice (TR4+/−) showed slower bladder cancer growth than wild-type mice (TR4+/+) induced by the carcinogenic chemicals. Moreover, TR4+/− mice showed a lower grade of histopathology than the control group. In conclusion, these results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment.https://www.frontiersin.org/articles/10.3389/fmolb.2021.670409/fulltesticular nuclear receptor 4bladder cancerapoptosisproliferationBcl-2 |
| spellingShingle | Huan Wang Wenqin Luo Xuliang Wang Dingwei Xue Liangliang Ren Li Xu Guangju Ge Liqun Xia Shicheng Yu Mingchao Wang Zhenwei Zhou Gonghui Li Haiyang Wu Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2 Frontiers in Molecular Biosciences testicular nuclear receptor 4 bladder cancer apoptosis proliferation Bcl-2 |
| title | Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2 |
| title_full | Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2 |
| title_fullStr | Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2 |
| title_full_unstemmed | Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2 |
| title_short | Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2 |
| title_sort | testicular nuclear receptor 4 regulates proliferation and apoptosis of bladder cancer via bcl 2 |
| topic | testicular nuclear receptor 4 bladder cancer apoptosis proliferation Bcl-2 |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.670409/full |
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