Effect of subcutaneous adipose tissue-associated CSRP2 on the progression of prostate cancer via the WDR5/USP44 pathway.

IF 3.6 3区 医学 Q2 ONCOLOGY
American journal of cancer research Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI:10.62347/AHQT5920
Juan Wang, Yuting Liang, Kaiwen Wang, Lihui Lin, Xia Peng, Weize Li, Yanning Li, Huanjin Liao, Jia Li, Longwei Qiao, Li Li
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引用次数: 0

Abstract

Elevated subcutaneous adipose tissue in obese men correlates strongly with a higher risk of aggressive prostate cancer and poor treatment outcomes, but the exact mechanism underlying the increased risk remains elusive. To address this question, we analyzed prostate cancer transcriptomic data from The Cancer Genome Atlas as well as single-cell RNA sequencing and tissue microarray data from prostate cancer cells. Subcutaneous adipose tissue-associated cysteine-rich protein 2 (CSRP2) was significantly downregulated in prostate cancer epithelial cells. Knockdown of CSRP2 promoted proliferation of prostate cancer cell lines DU145 and PC3, whereas the opposite effect was observed with CSRP2 overexpression. In vivo xenograft assays confirmed that CSRP2 overexpression inhibits the growth of prostate cancer cells. Importantly, co-immunoprecipitation and mass spectrometry assays confirmed that CSRP2 inhibits the deubiquitination of WD40 repeat protein 5 (WDR5) by ubiquitin-specific protease 44 (USP44). Overexpression of WDR5 reversed the growth inhibition of CSRP2 overexpression on prostate cancer cells. Altogether, our data indicate that CSRP2 suppresses prostate cancer cell proliferation via a CSRP2/WDR5/USP44 dependent pathway to control prostate cancer progression, suggesting a potential mechanism for prostate cancer treatment.

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来源期刊
自引率
3.80%
发文量
263
期刊介绍: The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.
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