TPH1 inhibits bladder tumorigenesis by targeting HIF-1α pathway in bladder cancer.

IF 0.4 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Asian Biomedicine Pub Date : 2024-09-20 eCollection Date: 2024-08-01 DOI:10.2478/abm-2024-0023
Jianwei Ren, Zhiting Mo, Xia Deng, Minghui Ren, Hailong Ren, Jie Jin, Huihui Zhang
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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.

TPH1 通过靶向膀胱癌中的 HIF-1α 通路抑制膀胱肿瘤发生。
背景:BCa 是最常见的泌尿系统癌症。据报道,TPH1与独特的肿瘤发生有关。然而,TPH1 在 BCa 中的作用仍有待明确:我们的目的是证明 TPH1 在 BCa 癌变和发展中的分子机制:在研究中,我们探讨了TPH1对T24细胞的影响。方法:在研究中,我们探讨了 TPH1 对 T24 细胞的影响,使用菌落形成、软琼脂和细胞增殖试验来确定细胞的存活和增殖能力。此外,还使用 CRISP-CAS9 分析了 TPH1-/- 细胞系,并进行了恢复实验。采用实时荧光定量 PCR(qPCR)和 Western 印迹法检测 HIF-1α mRNA 水平和 TPH1 蛋白:结果:肿瘤组织中 TPH1 的表达低于正常组织。集落形成、软琼脂和细胞增殖试验表明,TPH1过表达会降低细胞存活率。此外,缺乏 TPH1 会增加克隆数量。这些结果表明,TPH1 过表达会抑制细胞的存活率。此外,我们还发现,随着 TPH1 的增加,HIF-1α 的活性明显下调。TPH1-/-细胞中存活素的转录活性增加。然后,TPH1-/-细胞的增殖能力在LW6的处理下几乎与野生型水平相似,TPH1可能在抑制HIF-1α活性方面发挥了重要作用:综上所述,这些结果表明,增加 TPH1 的活性可通过 HIF-1α 通路抑制细胞的存活和增殖。TPH1 可能是人类 BCa 治疗的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Asian Biomedicine
Asian Biomedicine 医学-医学:研究与实验
CiteScore
1.20
自引率
0.00%
发文量
24
审稿时长
6-12 weeks
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.
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