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探索生物信息学工具以分析CDC6通过促进免疫浸润在多囊卵巢综合征进展为子宫内膜癌过程中的作用。

Exploring Bioinformatics Tools to Analyze the Role of CDC6 in the Progression of Polycystic Ovary Syndrome to Endometrial Cancer by Promoting Immune Infiltration.

作者信息

Song Yuhang, Zhang Jing, Li Yao, Cheng Lufeng, Song Hua, Zhang Yuhang, Du Guoqing, Yu Sunyue, Zou Yizhou, Xu Qi

机构信息

School of Basic Medicine, Xinjiang Medical University, Urumqi 830054, China.

School of Clinical Medicine, Xinjiang Medical University, Urumqi 830054, China.

出版信息

Int J Mol Sci. 2024 Dec 3;25(23):12974. doi: 10.3390/ijms252312974.

DOI:10.3390/ijms252312974
PMID:39684684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11640967/
Abstract

Cell division cycle 6 (CDC6) is essential for the initiation of DNA replication in eukaryotic cells and contributes to the development of various human tumors. Polycystic ovarian syndrome (PCOS) is a reproductive endocrine disease in women of childbearing age, with a significant risk of endometrial cancer (EC). However, the role of CDC6 in the progression of PCOS to EC is unclear. Therefore, we examined CDC6 expression in patients with PCOS and EC. We evaluated the relationship between CDC6 expression and its prognostic value, potential biological functions, and immune infiltrates in patients with EC. In vitro analyses were performed to investigate the effects of CDC6 knockdown on EC proliferation, migration, invasion, and apoptosis. CDC6 expression was significantly upregulated in patients with PCOS and EC. Moreover, this protein caused EC by promoting the aberrant infiltration of macrophages into the immune microenvironment in patients with PCOS. A functional enrichment analysis revealed that CDC6 exerted its pro-cancer and pro-immune cell infiltration functions via the PI3K-AKT pathway. Moreover, it promoted EC proliferation, migration, and invasion but inhibited apoptosis. This protein significantly reduced EC survival when mutated. These findings demonstrate that CDC6 regulates the progression of PCOS to EC and promotes immune infiltration.

摘要

细胞分裂周期6（CDC6）对于真核细胞中DNA复制的起始至关重要，并促进各种人类肿瘤的发展。多囊卵巢综合征（PCOS）是育龄期女性的一种生殖内分泌疾病，具有患子宫内膜癌（EC）的显著风险。然而，CDC6在PCOS进展为EC过程中的作用尚不清楚。因此，我们检测了PCOS和EC患者中CDC6的表达。我们评估了CDC6表达与其预后价值、潜在生物学功能以及EC患者免疫浸润之间的关系。进行体外分析以研究CDC6敲低对EC增殖、迁移、侵袭和凋亡的影响。PCOS和EC患者中CDC6表达显著上调。此外，这种蛋白质通过促进巨噬细胞异常浸润到PCOS患者的免疫微环境中而导致EC发生。功能富集分析表明，CDC6通过PI3K-AKT途径发挥其促癌和促免疫细胞浸润功能。此外，它促进了EC的增殖、迁移和侵袭，但抑制了凋亡。这种蛋白质发生突变时会显著降低EC的存活率。这些发现表明，CDC6调节PCOS向EC的进展并促进免疫浸润。

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LINC01088/miR-22/CDC6 Axis Regulates Prostate Cancer Progression by Activating the PI3K/AKT Pathway.
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