Abstract

BCa is the most common cancer of the urinary system. TPH1 has been reported to be associated with distinct tumorigenesis. However, the role of TPH1 in BCa remains to be clarified. Our aim is to demonstrate the molecular mechanism of TPH1 in BCa carcinogenesis and development. In research, we explored the effect of TPH1 on T24 cells. Colony formation, soft agar, and cell proliferation assays were used to determine the survival and proliferative capacity of cells. Moreover, TPH1-/- cell lines were analyzed using CRISP-CAS9, and the recovery experiment was conducted. Realtime fluorescence quantitative PCR (qPCR) and Western blot were used to detect HIF-1α mRNA levels and TPH1 protein. The TPH1 expression is lower in tumor tissues than in normal tissues. Colony formation, soft agar, and cell proliferation assays revealed that the overexpression of TPH1 declined cells survival. Moreover, the deficiency of TPH1 increased the number of clones. These results suggested that survival rate of TPH1 overexpression was repressed in cells. In addition, we found that HIF-1α activity was significantly downregulated with an increase in TPH1. The transcriptional activity of survivin was increased with TPH1-/- cells. Then, the proliferative ability of TPH1-/- cells was almost similar to the wild type levels with the treatment of LW6, TPH1 might play a major role to repress HIF-1α activity. Taken together, these results suggested that increasing TPH1 activity could inhibit survival and proliferation of cells via HIF-1α pathway. TPH1 may be a potential target for human BCa therapy.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.