STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc
SCL/TAL1 interrupting locus (STIL) regulates centriole replication and causes chromosome instability, which is closely related to malignant tumors. The purpose of our study was to investigate the role of STIL in bladder cancer (BC) tumorigenesis for the first time. The public database indicated that...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/23/5777 |
| _version_ | 1797463571387383808 |
|---|---|
| author | Hua Yu Liang Chen Xia Wang Feng Tang Ziyu Wan Hao Wang Qiqi Fu Zhizhuang Chen Jiageng Shi Xuan Hu Yisha Zuhaer Madanyeti Aersi Tao Liu Huangheng Tao Jianping Peng |
| author_facet | Hua Yu Liang Chen Xia Wang Feng Tang Ziyu Wan Hao Wang Qiqi Fu Zhizhuang Chen Jiageng Shi Xuan Hu Yisha Zuhaer Madanyeti Aersi Tao Liu Huangheng Tao Jianping Peng |
| author_sort | Hua Yu |
| collection | DOAJ |
| description | SCL/TAL1 interrupting locus (STIL) regulates centriole replication and causes chromosome instability, which is closely related to malignant tumors. The purpose of our study was to investigate the role of STIL in bladder cancer (BC) tumorigenesis for the first time. The public database indicated that STIL is highly expressed and correlated with the cell cycle in BC. Immunohistochemistry staining showed that STIL expression is significantly elevated in BC tissues compared with paracancer tissues. CRISPR-Cas9 gene editing technology was used to induce BC cells to express STIL-specific sgRNA, revealing a significantly delayed growth rate in STIL knockout BC cells. Moreover, cell cycle arrest in the G0/G1 phase was triggered by decreasing STIL, which led to delayed BC cell growth in vitro and in vivo. Mechanically, STIL knockout inhibited the PI3K/AKT/mTOR pathway and down-regulated the expression of c-myc. Furthermore, SC79 (AKT activating agent) partially reversed the inhibitory effects of STIL knockout on the proliferation and migration of BC cells. In conclusion, STIL enhanced the PI3K/AKT/mTOR pathway, resulting in increased expression of c-myc, ultimately promoting BC occurrence and progression. These results indicate that STIL might be a potential target for BC patients. |
| first_indexed | 2024-03-09T17:52:38Z |
| format | Article |
| id | doaj.art-bb5705be60c04fc58be9fd204382b74d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:52:38Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bb5705be60c04fc58be9fd204382b74d2023-11-24T10:38:30ZengMDPI AGCancers2072-66942022-11-011423577710.3390/cancers14235777STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-MycHua Yu0Liang Chen1Xia Wang2Feng Tang3Ziyu Wan4Hao Wang5Qiqi Fu6Zhizhuang Chen7Jiageng Shi8Xuan Hu9Yisha Zuhaer10Madanyeti Aersi11Tao Liu12Huangheng Tao13Jianping Peng14Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Public Health, Wuhan University Hospital, Wuhan University, Wuhan 430072, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaState Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Wuhan University, Wuhan 430070, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430061, ChinaSCL/TAL1 interrupting locus (STIL) regulates centriole replication and causes chromosome instability, which is closely related to malignant tumors. The purpose of our study was to investigate the role of STIL in bladder cancer (BC) tumorigenesis for the first time. The public database indicated that STIL is highly expressed and correlated with the cell cycle in BC. Immunohistochemistry staining showed that STIL expression is significantly elevated in BC tissues compared with paracancer tissues. CRISPR-Cas9 gene editing technology was used to induce BC cells to express STIL-specific sgRNA, revealing a significantly delayed growth rate in STIL knockout BC cells. Moreover, cell cycle arrest in the G0/G1 phase was triggered by decreasing STIL, which led to delayed BC cell growth in vitro and in vivo. Mechanically, STIL knockout inhibited the PI3K/AKT/mTOR pathway and down-regulated the expression of c-myc. Furthermore, SC79 (AKT activating agent) partially reversed the inhibitory effects of STIL knockout on the proliferation and migration of BC cells. In conclusion, STIL enhanced the PI3K/AKT/mTOR pathway, resulting in increased expression of c-myc, ultimately promoting BC occurrence and progression. These results indicate that STIL might be a potential target for BC patients.https://www.mdpi.com/2072-6694/14/23/5777STILbladder cancerPI3K/AKT/mTOR pathwayc-myccell cycle |
| spellingShingle | Hua Yu Liang Chen Xia Wang Feng Tang Ziyu Wan Hao Wang Qiqi Fu Zhizhuang Chen Jiageng Shi Xuan Hu Yisha Zuhaer Madanyeti Aersi Tao Liu Huangheng Tao Jianping Peng STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc Cancers STIL bladder cancer PI3K/AKT/mTOR pathway c-myc cell cycle |
| title | STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc |
| title_full | STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc |
| title_fullStr | STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc |
| title_full_unstemmed | STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc |
| title_short | STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc |
| title_sort | stil promotes tumorigenesis of bladder cancer by activating pi3k akt mtor signaling pathway and targeting c myc |
| topic | STIL bladder cancer PI3K/AKT/mTOR pathway c-myc cell cycle |
| url | https://www.mdpi.com/2072-6694/14/23/5777 |
| work_keys_str_mv | AT huayu stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT liangchen stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT xiawang stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT fengtang stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT ziyuwan stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT haowang stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT qiqifu stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT zhizhuangchen stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT jiagengshi stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT xuanhu stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT yishazuhaer stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT madanyetiaersi stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT taoliu stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT huanghengtao stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc AT jianpingpeng stilpromotestumorigenesisofbladdercancerbyactivatingpi3kaktmtorsignalingpathwayandtargetingcmyc |