Altered RBM10 subcellular localization relates to breast cancer via reducing p53 level and modulating immune microenvironment: Bioinformatics aided study

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-05-04 DOI:10.1016/j.genrep.2025.102246

Sheng Huang , Tairen Wang , Jianbin Chen

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引用次数: 0

Abstract

Aim

Despite significant progress in early diagnosis and treatment over the past few years, breast cancer (BC) accounts for the highest number of cancer-related deaths in the female population worldwide. Dysregulation of RBM10 has been observed in multiple types of cancers; however, the mechanism by which RBM10 alteration contributes to BC remains unclear. This study aimed to investigate the role of RBM10 in BC patients.

Materials and methods

Transcriptomic and proteomic data were obtained from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium. The RBM10 protein levels in tissue samples were downloaded from The Human Protein Atlas, and the phosphorylation status of RBM10 was obtained from the CPTAC database. The phosphorylation and subcellular localization of RBM10 were detected in BC cell lines. The impact of RBM10 on carcinogenesis was examined in BC cell lines using the MTT assay, flow cytometry analysis, and a xenograft mouse model. The role of RBM10 in the TME was analyzed using tumor and immune system interaction databases (TISIDB).

Results

Both the mRNA and protein levels of RBM10 were significantly upregulated in BC samples. After analyzing the survival data of 2976 patients with BC, we noticed that patients with higher RBM10 expression had a prolonged survival time. RBM10 protein leaked from the cell nucleus to the cytoplasm in the BC samples. Phosphorylation of S775 is a key factor modulating RBM10 subcellular localization in BC cells and regulating p53 degradation. RBM10 may function as an antitumor activator by repressing the expression of TGFBR1 and CD274, limiting the proportion of Th2 cells, and increasing the number of NK cells.

Conclusion

We identified for the first time that the re-localization of RBM10 is related to BC by regulating p53 degradation and modulating the immune microenvironment, which provides clues for improving the clinical treatment of BC.

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RBM10亚细胞定位改变通过降低p53水平和调节免疫微环境与乳腺癌相关：生物信息学辅助研究

尽管过去几年在早期诊断和治疗方面取得了重大进展，但乳腺癌（BC）在全球女性人口中占癌症相关死亡人数最多。RBM10的失调已在多种类型的癌症中观察到；然而，RBM10改变导致BC的机制尚不清楚。本研究旨在探讨RBM10在BC患者中的作用。材料和方法转录组学和蛋白质组学数据来自癌症基因组图谱和临床蛋白质组学肿瘤分析联盟。从The Human protein Atlas下载组织样品中的RBM10蛋白水平，从CPTAC数据库获取RBM10的磷酸化状态。在BC细胞系中检测到RBM10的磷酸化和亚细胞定位。通过MTT实验、流式细胞术分析和异种移植小鼠模型，研究了RBM10对BC细胞系癌变的影响。使用肿瘤和免疫系统相互作用数据库（TISIDB）分析RBM10在TME中的作用。结果BC样品中RBM10 mRNA和蛋白水平均显著上调。在分析2976例BC患者的生存数据后，我们发现RBM10表达较高的患者生存时间较长。在BC样本中，RBM10蛋白从细胞核渗漏到细胞质。S775的磷酸化是调节BC细胞中RBM10亚细胞定位和调节p53降解的关键因素。RBM10可能通过抑制TGFBR1和CD274的表达，限制Th2细胞的比例，增加NK细胞的数量来发挥抗肿瘤激活剂的作用。结论首次发现RBM10的再定位通过调控p53降解和调节免疫微环境与BC相关，为改善BC的临床治疗提供线索。

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

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.