RBM15B 通过 PCNA m6A 修饰促进前列腺癌细胞增殖

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Biochemistry and Biophysics Pub Date : 2024-10-03 DOI:10.1007/s12013-024-01558-5
Huan Cheng, Zeyu Chen, Yong Wang, Chengjian Ji, Junqi Wang, Ninghong Song
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引用次数: 0

摘要

前列腺癌(PC)是男性最常见的癌症,其特征是前列腺内细胞的异常增殖。本研究探讨了 RNA 结合基序蛋白 15B (RBM15B) 在 PC 中的作用。利用Starbase数据库预测了PC患者中RBM15B的表达水平。检测了PC细胞中RBM15B的表达和增殖细胞核抗原(PCNA)的表达。在敲除 RBM15B 后,进行了细胞增殖试验。对 PC 细胞中的 N6-甲基腺苷(m6A)水平进行了定量,并进行了 RNA 免疫沉淀,以分析 m6A 与 PCNA mRNA 上的 YTH N-methyladenosine RNA 结合蛋白 1(YTHDF1)的结合情况。为了验证 RBM15B 的作用,建立了裸鼠异种移植模型。研究结果显示 RBM15B 在 PC 中上调。敲除 RBM15B 会导致增殖、集落形成和 EdU 阳性细胞减少。力学分析表明,RBM15B 促进了 PCNA mRNA 的 m6A 修饰,导致 m6A 甲基化增加。YTHDF1 与 PCNA mRNA 上的这些 m6A 位点结合,从而使其稳定。此外,过表达 PCNA 可减轻 RBM15B 敲除对 PC 细胞增殖的影响。总之,RBM15B通过YTHDF1介导的m6A修饰增强了PCNA mRNA的稳定性,从而促进了PC细胞的增殖。
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RBM15B Promotes Prostate Cancer Cell Proliferation via PCNA m6A Modification.

Prostate cancer (PC) is the most frequently occurring cancer in men, characterized by the abnormal proliferation of cells within the prostate gland. This study explores the role of RNA binding motif protein 15B (RBM15B) in PC. RBM15B expression levels in PC patients were predicted using the Starbase database. The expression of RBM15B and proliferating cell nuclear antigen (PCNA) expression in PC cells was detected. Following RBM15B knockdown, cell proliferation assays were conducted. N6-methyladenosine (m6A) levels in PC cells were quantified, and RNA immunoprecipitation was performed to analyze the binding of m6A and YTH N-methyladenosine RNA binding protein 1 (YTHDF1) on PCNA mRNA. The stability of PCNA mRNA was assessed after treatment with actinomycin D. An in vivo nude mouse xenograft model was created to validate the role of RBM15B. The findings revealed the upregulation of RBM15B in PC. RBM15B knockdown resulted in decreased proliferation, colony formation, and EdU-positive cells. Mechanical analysis showed that RBM15B facilitated m6A modification of PCNA mRNA, leading to increasing m6A methylation. YTHDF1 bound to these m6A sites on PCNA mRNA, thus stabilizing it. Furthermore, PCNA overexpression mitigated the effects of RBM15B knockdown on PC cell proliferation. In conclusion, RBM15B promotes PC cell proliferation by enhancing the stability of PCNA mRNA through YTHDF1-mediated m6A modification.

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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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