肿瘤细胞源性DNASE2B通过分泌PSA介导M2巨噬细胞浸润促进前列腺癌进展

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Yulin Dai , Junkai Xu , Yunhui Zhao , Dongdong Ke , Qing Gao , Qisong Chen
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引用次数: 0

摘要

本研究旨在探讨dna e2b(脱氧核糖核酸酶II β)的作用,这是一种在前列腺癌(PCa)中特异性过表达的基因,其驱动疾病进展的机制尚不清楚。我们使用Western blotting、q-PCR和免疫组织化学分析了TCGA数据库和PCa细胞系/组织中的DNASE2B表达。通过细胞划痕、Transwell和皮下肿瘤试验评估生物学功能。使用TISCH2、GEO数据集和Timer2.0研究免疫微环境的变化。通过Transwell、原位模型、免疫组织化学、免疫荧光和流式细胞术验证M2巨噬细胞浸润。鉴定下游靶点,并使用q-PCR、Western blotting和ELISA验证DNASE2B-PSA关系。体内模型探讨了M2调控的机制。结果显示,DNASE2B在前列腺癌组织中的表达明显高于癌旁正常组织。在体外和体内,沉默PC3细胞中的DNASE2B均能显著抑制PCa的恶性进展。DNASE2B表达与M2巨噬细胞浸润呈强正相关,通过影响PSA分泌间接促进M2巨噬细胞浸润,加速PCa进展。综上所述,PCa细胞中高表达的DNASE2B通过增加PSA分泌,促进M2巨噬细胞浸润,从而推动PCa的恶性进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tumor cell-derived DNASE2B mediates M2 macrophage infiltration to promote prostate cancer progression through the PSA secretion
This study sought to explore the role of DNASE2B (deoxyribonuclease II beta), a gene specifically overexpressed in prostate cancer (PCa) whose mechanism in driving disease progression remains unclear. We analyzed DNASE2B expression in the TCGA database and PCa cell lines/tissues using Western blotting, q-PCR, and immunohistochemistry. Biological functions were assessed via cell scratch, Transwell, and subcutaneous tumor assays. Immune microenvironment changes were investigated using TISCH2, GEO datasets, and Timer2.0. M2 macrophage infiltration was validated via Transwell, orthotopic models, Immunohistochemistry and immunofluorescence and flow cytometry. Downstream targets were identified, and the DNASE2B-PSA relationship was verified using q-PCR, Western blotting, and ELISA. In vivo models explored the mechanism of M2 regulation. Results showed that DNASE2B expression was significantly higher in PCa tissues than in adjacent normal tissues. Silencing DNASE2B in PC3 cells markedly inhibited malignant progression of PCa both in vitro and in vivo. DNASE2B expression was strongly positively correlated with M2 macrophage infiltration, and it indirectly promoted M2 macrophage infiltration and accelerated PCa progression by affecting PSA secretion. In summary, high DNASE2B expression in PCa cells enhances M2 macrophage infiltration by increasing PSA secretion, thereby driving malignant progression of PCa.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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