Exploring the role of eIF3m in prostate cancer: regulation of c-Myc signaling pathway and therapeutic implications.

IF 2 4区 医学 Q3 ONCOLOGY
Dongdong Guo, Cheng Ma, Jianyi Gu, Xinyu Zhai, Xinlin Chen, Guanqun Ju, Chuanmin Chu, Xiangyang Zhan, Tao Wang, Mingyue Tan, Dongliang Xu
{"title":"Exploring the role of eIF3m in prostate cancer: regulation of c-Myc signaling pathway and therapeutic implications.","authors":"Dongdong Guo, Cheng Ma, Jianyi Gu, Xinyu Zhai, Xinlin Chen, Guanqun Ju, Chuanmin Chu, Xiangyang Zhan, Tao Wang, Mingyue Tan, Dongliang Xu","doi":"10.4149/neo_2024_240603N242","DOIUrl":null,"url":null,"abstract":"<p><p>Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in males, and there are currently few effective therapeutic targets following hormone therapy resistance. Subunits of eukaryotic initiation factor 3 (eIF3) have been implicated in the progression of various cancers. This study aims to investigate the biological functions of the eIF3m subunit in PCa and assess its potential as a novel therapeutic target for treatment. We utilized open-access datasets and patient tissues to analyze the expression and prognostic value of eIF3m in PCa. To explore the role of eIF3m in PCa growth, we established eIF3m knockdown models in PC3 and 22Rv1 cells for both in vitro and in vivo studies. Gene set enrichment analysis (GSEA) was utilized to identify signaling pathways regulated by eIF3m in PCa. Additionally, western blotting and immunochemistry were used to confirm the regulation of c-Myc signaling by eIF3m in PCa. Our results indicated that eIF3m expression was elevated in PCa tissues, with higher levels correlating with an increased risk of biochemical recurrence following radical prostatectomy. Both in vitro and in vivo experiments demonstrated that inhibiting eIF3m significantly impeded the growth of PCa cells. GSEA and immunochemistry further revealed that high eIF3m expression contributed to the activation of c-Myc signaling in PCa patients. Notably, the downregulation of eIF3m resulted in a significant decrease in the expression of c-Myc mRNA and protein in PCa cells. Overall, our findings suggest that eIF3m inhibition significantly suppressed PCa cell growth and c-Myc signaling, indicating that eIF3m is a promising therapeutic target for PCa patients.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 5","pages":"442-450"},"PeriodicalIF":2.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neoplasma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4149/neo_2024_240603N242","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in males, and there are currently few effective therapeutic targets following hormone therapy resistance. Subunits of eukaryotic initiation factor 3 (eIF3) have been implicated in the progression of various cancers. This study aims to investigate the biological functions of the eIF3m subunit in PCa and assess its potential as a novel therapeutic target for treatment. We utilized open-access datasets and patient tissues to analyze the expression and prognostic value of eIF3m in PCa. To explore the role of eIF3m in PCa growth, we established eIF3m knockdown models in PC3 and 22Rv1 cells for both in vitro and in vivo studies. Gene set enrichment analysis (GSEA) was utilized to identify signaling pathways regulated by eIF3m in PCa. Additionally, western blotting and immunochemistry were used to confirm the regulation of c-Myc signaling by eIF3m in PCa. Our results indicated that eIF3m expression was elevated in PCa tissues, with higher levels correlating with an increased risk of biochemical recurrence following radical prostatectomy. Both in vitro and in vivo experiments demonstrated that inhibiting eIF3m significantly impeded the growth of PCa cells. GSEA and immunochemistry further revealed that high eIF3m expression contributed to the activation of c-Myc signaling in PCa patients. Notably, the downregulation of eIF3m resulted in a significant decrease in the expression of c-Myc mRNA and protein in PCa cells. Overall, our findings suggest that eIF3m inhibition significantly suppressed PCa cell growth and c-Myc signaling, indicating that eIF3m is a promising therapeutic target for PCa patients.

探索 eIF3m 在前列腺癌中的作用:c-Myc 信号通路的调控和治疗意义。
前列腺癌(PCa)是男性中最常诊断出的恶性肿瘤,目前几乎没有有效的治疗靶点,因为激素疗法会产生抗药性。真核细胞启动因子 3(eIF3)的亚基与各种癌症的进展有牵连。本研究旨在调查 eIF3m 亚基在 PCa 中的生物学功能,并评估其作为新型治疗靶点的潜力。我们利用开放存取的数据集和患者组织分析了eIF3m在PCa中的表达和预后价值。为了探索eIF3m在PCa生长中的作用,我们在PC3和22Rv1细胞中建立了eIF3m敲除模型,用于体外和体内研究。我们利用基因组富集分析(GSEA)确定了 PCa 中受 eIF3m 调控的信号通路。此外,我们还采用了免疫印迹和免疫化学方法来证实 eIF3m 对 PCa 中 c-Myc 信号的调控作用。我们的研究结果表明,eIF3m在PCa组织中的表达量升高,而较高的表达量与根治性前列腺切除术后生化复发风险的增加有关。体外和体内实验均表明,抑制 eIF3m 能显著抑制 PCa 细胞的生长。GSEA和免疫化学进一步显示,eIF3m的高表达有助于激活PCa患者体内的c-Myc信号。值得注意的是,eIF3m的下调导致PCa细胞中c-Myc mRNA和蛋白的表达显著下降。总之,我们的研究结果表明,抑制eIF3m能明显抑制PCa细胞的生长和c-Myc信号转导,这表明eIF3m是治疗PCa患者的一个很有前景的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Neoplasma
Neoplasma 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
238
审稿时长
3 months
期刊介绍: The journal Neoplasma publishes articles on experimental and clinical oncology and cancer epidemiology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信