{"title":"TPH1 inhibits bladder tumorigenesis by targeting HIF-1α pathway in bladder cancer.","authors":"Jianwei Ren, Zhiting Mo, Xia Deng, Minghui Ren, Hailong Ren, Jie Jin, Huihui Zhang","doi":"10.2478/abm-2024-0023","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>Our aim is to demonstrate the molecular mechanism of TPH1 in BCa carcinogenesis and development.</p><p><strong>Methods: </strong>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<sup>-/-</sup> cell lines were analyzed using <i>CRISP-CAS9</i>, 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.</p><p><strong>Results: </strong>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<sup>-/-</sup> cells. Then, the proliferative ability of TPH1<sup>-/-</sup> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8501,"journal":{"name":"Asian Biomedicine","volume":"18 4","pages":"171-179"},"PeriodicalIF":0.4000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414775/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Biomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2478/abm-2024-0023","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Objectives: Our aim is to demonstrate the molecular mechanism of TPH1 in BCa carcinogenesis and development.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍:
Asian Biomedicine: Research, Reviews and News (ISSN 1905-7415 print; 1875-855X online) is published in one volume (of 6 bimonthly issues) a year since 2007. [...]Asian Biomedicine is an international, general medical and biomedical journal that aims to publish original peer-reviewed contributions dealing with various topics in the biomedical and health sciences from basic experimental to clinical aspects. The work and authorship must be strongly affiliated with a country in Asia, or with specific importance and relevance to the Asian region. The Journal will publish reviews, original experimental studies, observational studies, technical and clinical (case) reports, practice guidelines, historical perspectives of Asian biomedicine, clinicopathological conferences, and commentaries
Asian biomedicine is intended for a broad and international audience, primarily those in the health professions including researchers, physician practitioners, basic medical scientists, dentists, educators, administrators, those in the assistive professions, such as nurses, and the many types of allied health professionals in research and health care delivery systems including those in training.