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CCR4-NOT 转录复合体亚基 7(CNOT7)蛋白与白细胞相关免疫球蛋白样受体-1 在乳腺癌进展中的作用:临床机制见解与计算机模拟治疗潜力

英文原题:CCR4-NOT Transcription Complex Subunit 7 (CNOT7) Protein and Leukocyte-Associated Immunoglobulin-like Receptor-1 in Breast Cancer Progression: Clinical Mechanistic Insights and In Silico Therapeutic Potential.

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CCR4-NOT Transcription Complex Subunit 7 (CNOT7) Protein and Leukocyte-Associated Immunoglobulin-like Receptor-1 in Breast Cancer Progression: Clinical Mechanistic Insights and In Silico Therapeutic Potential.

PubMed 2025/07/24(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

转移性乳腺癌(BC)的扩散凸显了对新型预后生物标志物的需求。本研究探讨了CCR4-NOT转录复合体亚基7(CNOT7)和白细胞相关免疫球蛋白样受体-1(LAIR-1)在BC进展和自然杀伤(NK)细胞抵抗中的作用。

在本研究中,分析了90例女性BC患者(46例非转移性,44例转移性)。通过ELISA检测血清中CNOT7和LAIR-1蛋白水平,通过免疫组化(IHC)检测组织中CNOT7表达。计算机工具探索了相关通路。计算分析,包括计算机生物信息学和分子对接,探索了基因功能、相互作用以及与CNOT7和LAIR-1的配体结合。转移性患者血清CNOT7水平显著升高(均值4.710)相较于非转移性患者(均值3.229,p < 0.0001)。相反,转移性患者血清LAIR-1水平显著降低(均值56.779)相较于非转移性患者(均值67.544,p < 0.0001)。50%(45/90)的病例中发现高CNOT7,与更高的肿瘤分级、激素受体阴性和淋巴结受累增加相关。CNOT7升高和LAIR-1降低与更差的总生存期相关。通路分析将CNOT7与PI3K/AKT/mTOR通路联系起来。计算结果阐明了CNOT7的细胞作用、LAIR-1/CNOT7的基因/蛋白相互作用网络以及不同的配体结合谱。高CNOT7水平与晚期BC分期和不良临床结局相关,提示其作为预后生物标志物的实用性。CNOT7与LAIR-1之间的反向关系为BC进展和免疫逃逸提供了机制见解,计算机研究进一步支持了这一点。

展开英文摘要原文

Metastatic breast cancer (BC) spread underscores the need for novel prognostic biomarkers.

This study investigated CCR4-NOT Transcription Complex Subunit 7 (CNOT7) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) in BC progression and natural killer (NK) cell resistance. In the current study, 90 female BC patients (46 non-metastatic, 44 metastatic) were analyzed. CNOT7 and LAIR-1 protein levels were measured in serum via ELISA and CNOT7 expression in tissue by immunohistochemistry (IHC). In silico tools explored related pathways. Computational analyses, including in silico bioinformatics and molecular docking, explored gene functions, interactions, and ligand binding to CNOT7 and LAIR-1. CNOT7 serum levels were significantly elevated in metastatic patients (mean 4. 710) versus non-metastatic patients (mean 3. 229, p < 0. 0001). Conversely, LAIR-1 serum levels were significantly lower in metastatic (mean 56.

779) versus non-metastatic patients (mean 67. 544, p < 0. 0001). High CNOT7 was found in 50% (45/90) of cases, correlating with higher tumor grade, hormone receptor negativity, and increased lymph node involvement. Elevated CNOT7 and lower LAIR-1 levels were associated with worse overall survival. Pathway analysis linked CNOT7 to the PI3K/AKT/mTOR pathway.

Computational findings elucidated CNOT7's cellular roles, gene/protein interaction networks for LAIR-1/CNOT7, and distinct ligand binding profiles. High CNOT7 levels are associated with advanced BC stages and poor clinical outcomes, which suggests its utility as a prognostic biomarker. The inverse relationship between CNOT7 and LAIR-1 provides mechanistic insights into BC progression and immune evasion, further supported by in silico investigations.

论文信息

作者
Elanany MM、Mostafa D、Hady AA、Abd Allah MYY、Ahmed NS、Elghazawy NH、Sippl W、Yamamoto T
单位
Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt.Egypt
期刊
International journal of molecular sciences2025 Jul 24
原文标识
PubMed 40806280 · DOI 10.3390/ijms26157141