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YY1 通过靶向 FN1/PI3K/AKT 通路促进 DCUN1D5 的转录激活，从而促进三阴性乳腺癌的进展。

YY1 mediated DCUN1D5 transcriptional activation promotes triple-negative breast cancer progression by targeting FN1/PI3K/AKT pathway.

机构信息

Department of Breast Surgery, Fujian Medical University Union Hospital, No.29, Xin Quan Road, Gulou District, Fuzhou, 350001, Fujian Province, China.

Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian Province, China.

出版信息

Biol Direct. 2024 Jun 3;19(1):42. doi: 10.1186/s13062-024-00481-2.

DOI:10.1186/s13062-024-00481-2
PMID:38831379
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11145835/
Abstract

Triple-negative breast cancer (TNBC) is more aggressive and has a higher metastasis rate compared with other subtypes of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is now the only available systemic treatment for TNBC. However, some patients might still develop drug resistance and have poor prognosis. Therefore, novel molecular biomarkers and new treatment targets are urgently needed for patients with TNBC. To provide molecular insights into TNBC progression, we investigated the function and the underlying mechanism of Defective in cullin neddylation 1 domain containing 5 (DCUN1D5) in the regulation of TNBC. By TCGA dataset and surgical specimens with immunohistochemical (IHC) staining method, DCUN1D5 was identified to be significantly upregulated in TNBC tumor tissues and negatively associated with prognosis. A series of in vitro and in vivo experiments were performed to confirm the oncogenic role of DCUN1D5 in TNBC. Overexpression of FN1 or PI3K/AKT activator IGF-1 could restore the proliferative and invasive ability induced by DCUN1D5 knockdown and DCUN1D5 could act as a novel transcriptional target of transcription factor Yin Yang 1 (YY1). In conclusion, YY1-enhanced DCUN1D5 expression could promote TNBC progression by FN1/PI3K/AKT pathway and DCUN1D5 might be a potential prognostic biomarker and therapeutic target for TNBC treatment.

摘要

三阴性乳腺癌（TNBC）比其他乳腺癌亚型更具侵袭性，转移率更高。由于缺乏药物靶向受体，化疗现在是 TNBC 唯一可用的全身治疗方法。然而，一些患者可能仍然会产生耐药性，预后不良。因此，迫切需要针对 TNBC 患者的新型分子生物标志物和新的治疗靶点。为了深入了解 TNBC 的进展，我们研究了 Cullin 连接酶 neddylation 1 结构域缺失 5（DCUN1D5）在调节 TNBC 中的功能和潜在机制。通过 TCGA 数据集和免疫组织化学（IHC）染色方法的手术标本，发现 DCUN1D5 在 TNBC 肿瘤组织中显著上调，与预后呈负相关。进行了一系列体外和体内实验来证实 DCUN1D5 在 TNBC 中的致癌作用。FN1 或 PI3K/AKT 激活剂 IGF-1 的过表达可以恢复 DCUN1D5 敲低诱导的增殖和侵袭能力，并且 DCUN1D5 可以作为转录因子 Yin Yang 1（YY1）的新型转录靶标。总之，YY1 增强的 DCUN1D5 表达可以通过 FN1/PI3K/AKT 通路促进 TNBC 的进展，并且 DCUN1D5 可能是 TNBC 治疗的潜在预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf52/11145835/aacf1e29e6bb/13062_2024_481_Fig7_HTML.jpg
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Am J Transl Res. 2022 Apr 15;14(4):2550-2566. eCollection 2022.
3
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4
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