Phosphoribosyl pyrophosphate synthetases 2 knockdown inhibits prostate cancer progression by suppressing cell cycle and inducing cell apoptosis
| Autor: | Xiangming Mao, Fangpeng Shu, Chun Li, Chuan-Fan Zhong, Daojun Lv, Hui Qiao, Yaguang Zou, Rongwei Xing, Xiao Tan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gene knockdown Chemistry Cell growth Phosphoribosyl pyrophosphate proliferation Phosphoribosyl pyrophosphate synthetase 2 apoptosis Cell cycle medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Real-time polymerase chain reaction Oncology Apoptosis 030220 oncology & carcinogenesis Cancer research medicine prostate cancer Signal transduction Carcinogenesis Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | Phosphoribosyl pyrophosphate synthetases 2 (PRPS2) protein function as nucleotide synthesis enzyme that plays vital roles in cancer biology. However, the expression profile and function of PRPS2 in prostate cancer (PCa) remain to be identified. Here we investigated the expression of PRPS2 protein in human PCa and paired normal tissues by immunohistochemistry, meanwhile the regulatory effects on cell proliferation, apoptosis and growth of xenograft tumors in nude mice were evaluated in PCa cells with PRPS2 depletion. Moreover, the signaling pathways were also explored by western blot analysis and quantitative polymerase chain reaction assays. We found that PRPS2 was dramatically upregulated in prostate adenocarcinoma tissues in comparison with normal tissues, and that increased PRPS2 was linked intimately to advanced clinical stage and pT status. Functional experiments showed that knockdown of PRPS2 significantly suppressed cell growth both in vitro and in vivo. In addition, depletion of PRPS2 induced G1 phase cell cycle arrest and elevated cell apoptosis. Silencing of PRPS2 resulted in the decreased expression of Bcl‑2 and cyclinD1 and increased levels of Bax, cleavage of caspases‑3, caspases‑9 and PARP. Furthermore, we also detected PRPS2 expression was significantly induced after DHT treatment, which implied the important role of PRPS2 in oncogenesis of PCa. Taken together, our findings elucidated that PRPS2 may be a potential novel candidate for PCa therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|