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微小RNA-200c重编程成纤维细胞以重现乳腺癌进展过程中癌症相关成纤维细胞的表型。

MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression.

作者信息

Lin Zhao, Roche Megan E, Díaz-Barros Víctor, Domingo-Vidal Marina, Whitaker-Menezes Diana, Tuluc Madalina, Uppal Guldeep, Caro Jaime, Curry Joseph M, Martinez-Outschoorn Ubaldo

机构信息

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Immunology, Microenvironment & Metastasis Program, Wistar Institute, Philadelphia, Pennsylvania, USA.

出版信息

Cell Stress. 2024 Mar 11;8:1-20. doi: 10.15698/cst2024.03.293. eCollection 2024.

DOI:10.15698/cst2024.03.293
PMID:38476765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10927306/
Abstract

Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma cell resistance to apoptosis, proliferation and immunosuppression, leading to primary tumor growth, metastases, and resistance to immuno-chemotherapy. Conversely, miR-200c inhibition in fibroblasts restrains tumor growth with abated oxidative stress and an anti-tumorigenic immune environment. This work determines the mechanisms by which MET in CAFs via miR-200c transcriptional enrichment with DNA demethylation triggered by oxidative stress promotes cancer progression. CAFs undergoing MET trans-differentiation and senescence coordinate heterotypic signaling that may be targeted as an anti-cancer strategy.

摘要

间充质-上皮可塑性驱动癌症相关成纤维细胞（CAFs）中的癌症进展，其机制尚未明确。这项研究确定了人类乳腺癌中一组CAFs，它们表现出间充质-上皮转化（MET）或具有高miR-200c表达的上皮样特征。成纤维细胞中miR-200c的过表达足以驱动乳腺癌的侵袭性。肿瘤微环境中的氧化应激通过DNA去甲基化诱导miR-200c。蛋白质组学、RNA测序和功能分析表明，miR-200c是通过下调COMMD1对NFκB-HIF信号通路的新型正向调节因子，并刺激促肿瘤炎症和糖酵解。通过miR-200c将成纤维细胞重编程为MET可降低干性并诱导衰老表型。CAFs中的这种促肿瘤特征促进癌细胞对凋亡、增殖和免疫抑制的抵抗，导致原发性肿瘤生长、转移以及对免疫化疗的抵抗。相反，抑制成纤维细胞中的miR-200c可减轻氧化应激和抗肿瘤免疫环境，从而抑制肿瘤生长。这项研究确定了通过氧化应激触发的DNA去甲基化使miR-200c转录富集，从而使CAFs发生MET促进癌症进展的机制。经历MET转分化和衰老的CAFs协调异型信号传导，这可能成为一种抗癌策略的靶点。

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Sci Data. 2022 Mar 23;9(1):96. doi: 10.1038/s41597-022-01236-2.
3
Senescent tumor cells: an overlooked adversary in the battle against cancer.
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Exp Mol Med. 2021 Dec;53(12):1834-1841. doi: 10.1038/s12276-021-00717-5. Epub 2021 Dec 16.
4
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EMBO J. 2021 Jun 1;40(11):e107333. doi: 10.15252/embj.2020107333. Epub 2021 May 5.
5
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Biochim Biophys Acta Mol Basis Dis. 2020 Dec 1;1866(12):165962. doi: 10.1016/j.bbadis.2020.165962. Epub 2020 Sep 10.
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