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- Title
STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc.
- Authors
Yu, Hua; Chen, Liang; Wang, Xia; Tang, Feng; Wan, Ziyu; Wang, Hao; Fu, Qiqi; Chen, Zhizhuang; Shi, Jiageng; Hu, Xuan; Zuhaer, Yisha; Aersi, Madanyeti; Liu, Tao; Tao, Huangheng; Peng, Jianping
- Abstract
Simple Summary: Currently; there are no reports on the role of STIL in bladder cancer. Using public databases; we observed that STIL is highly expressed in bladder cancer and is closely related to the cell cycle. The results of tumor formation experiments on UMUC3 and T24 bladder cancer cell lines indicate that STIL promotes the growth of bladder cancer cells in vivo and in vitro. Mechanistically, the cell cycle after STIL knockout was arrested in the G0/G1 phase; and cell cycle-related proteins (cyclin D1 and CDK2/4/6) were also reduced. RNA-seq results and immunoblotting experiments confirmed that STIL enhanced the PI3K/AKT/mTOR pathway, resulting in increased c-myc expression which ultimately promoted the occurrence and progression of bladder cancer. Our results suggest that STIL may be a promising potential therapeutic target for bladder cancer. 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.
- Subjects
BLADDER tumors; IN vitro studies; IN vivo studies; PHOSPHOTRANSFERASES; ANIMAL experimentation; MTOR inhibitors; RNA; CELLULAR signal transduction; CELL cycle; IMMUNOBLOTTING; TUMOR markers
- Publication
Cancers, 2022, Vol 14, Issue 23, p5777
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers14235777