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含三联基序蛋白28(TRIM28)在乳腺浸润性癌患者病情进展、预后及治疗中的表达及虫草素抑制作用

Tripartite motif-containing 28 (TRIM28) expression and cordycepin inhibition in progression, prognosis, and therapeutics of patients with breast invasive carcinoma.

作者信息

Li Dabing, Cheng Jingliang, Zhang Wenqian, Zhang Lianmei, Maghsoudloo Mazaher, Fu Jiewen, Liu Xiaoyan, Xiao Xiuli, Wei Chunli, Fu Junjiang

机构信息

Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China.

School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, Sichuan Province, China.

出版信息

J Cancer. 2024 Jun 11;15(13):4374-4385. doi: 10.7150/jca.95876. eCollection 2024.

Abstract

Breast cancer (BC) is the most common tumor in women worldwide. TRIM28 (RNF96) plays pleiotropic biological functions, such as silencing target genes, facilitating DNA repair, stimulating cellular proliferation and differentiation, and contributing to cancer progression. TRIM28 plays an increasingly crucial role in cancer, but its impact on BC, including breast invasive carcinoma, remains poorly understood. In the current study, analyses of online databases, quantitative real-time quantitative PCR, immunohistochemistry, and western blotting were performed on patients with breast invasive carcinoma (BRCA). Cordycepin (CD) was used to monitor BC progression and TRIM28 expression . As a result, we observed that TRIM28 is highly expressed in breast invasive carcinoma tissues compared with the corresponding normal tissues and is correlated with metastatic / invasive progression. High expression of TRIM28 might serve as a prognostic marker for long-term survival in triple-negative BC, advanced BC, or breast invasive carcinoma. Although TRIM28 methylation in tumor tissues of breast invasive carcinoma is not significantly changed compared to the matched normal tissues, the expressions and methylation of TRIM28 are significantly reversely correlated. TRIM28 expression was inhibited by CD in the mouse model, indicating its role in preventing BC progression. Thus, TRIM28 might be a potentially valuable molecular target for forecasting the progression / prognosis of patients with breast invasive carcinoma. CD, which represses BC growth/metastasis, may be involved partially through suppressing TRIM28 expression.

摘要

乳腺癌(BC)是全球女性中最常见的肿瘤。TRIM28(RNF96)具有多种生物学功能,如使靶基因沉默、促进DNA修复、刺激细胞增殖和分化以及促进癌症进展。TRIM28在癌症中发挥着越来越关键的作用,但其对包括乳腺浸润性癌在内的乳腺癌的影响仍知之甚少。在本研究中,对乳腺浸润性癌(BRCA)患者进行了在线数据库分析、定量实时定量PCR、免疫组织化学和蛋白质印迹分析。使用虫草素(CD)来监测乳腺癌进展和TRIM28表达。结果,我们观察到与相应的正常组织相比,TRIM28在乳腺浸润性癌组织中高表达,并且与转移/侵袭进展相关。TRIM28的高表达可能作为三阴性乳腺癌、晚期乳腺癌或乳腺浸润性癌长期生存的预后标志物。尽管与匹配的正常组织相比,乳腺浸润性癌肿瘤组织中的TRIM28甲基化没有显著变化,但TRIM28的表达和甲基化呈显著负相关。在小鼠模型中,CD抑制了TRIM28的表达,表明其在预防乳腺癌进展中的作用。因此,TRIM28可能是预测乳腺浸润性癌患者进展/预后的潜在有价值的分子靶点。抑制乳腺癌生长/转移的CD可能部分通过抑制TRIM28表达而发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7c7/11212093/1ae35eba06c6/jcav15p4374g001.jpg

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