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通过单细胞测序和 schottenol 干预揭示 MDH1 在乳腺癌耐药中的作用

英文原题:Unveiling the role of MDH1 in breast cancer drug resistance through single-cell sequencing and schottenol intervention.

查看英文原题

Unveiling the role of MDH1 in breast cancer drug resistance through single-cell sequencing and schottenol intervention.

PubMed 2025/01/14(内容时间) Cell Signal Q2 · IF 4.7(JCR 2025)

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中文摘要

本研究利用单细胞RNA测序数据揭示乳腺癌与正常上皮细胞的转录组特征。通过严格的质量控制和批次效应校正,鉴定出9个显著细胞群体。基于PAM50方法和临床亚型对乳腺癌上皮细胞进一步分类,突显了三阴性乳腺癌(TNBC)与非三阴性乳腺癌(NTNBC)之间的显著异质性。研究还分析了乳腺癌免疫微环境中的髓系细胞和TIL(肿瘤浸润淋巴细胞)(TILs),鉴定出14个TIL亚群并评估其在不同患者中的比例变化。CellChat工具揭示了肿瘤微环境中复杂的细胞通讯网络,显示TNBC与NTNBC患者在通讯强度和模式上存在显著差异。

此外,证实了衰老相关基因MDH1在乳腺癌中的关键调控作用,并探讨了其对药物敏感性的影响。最后,发现植物甾醇Schottenol通过下调MDH1表达抑制乳腺癌细胞增殖,并增强对紫杉醇的敏感性。这些发现为MDH1作为治疗靶点提供了新见解,并提示Schottenol可作为克服乳腺癌耐药性的潜在策略。

展开英文摘要原文

This study utilizes single-cell RNA sequencing data to reveal the transcriptomic characteristics of breast cancer and normal epithelial cells. Nine significant cell populations were identified through stringent quality control and batch effect correction.

Further classification of breast cancer epithelial cells based on the PAM50 method and clinical subtypes highlighted significant heterogeneity between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (NTNBC).

The study also analyzed myeloid cells and tumor-infiltrating lymphocytes (TILs) within the breast cancer immune microenvironment, identifying 14 TIL subpopulations and assessing their proportion variations across different patients. The CellChat tool revealed a complex cellular communication network within the tumor microenvironment, showing notable differences in communication intensity and patterns between TNBC and NTNBC patients.

Additionally, the key regulatory role of the senescence-associated gene MDH1 in breast cancer was confirmed, and its impact on drug sensitivity was explored.

Finally, it was discovered that the phytosterol Schottenol inhibits breast cancer cell proliferation by downregulating MDH1 expression and enhances sensitivity to paclitaxel.

These findings provide new insights into MDH1 as a therapeutic target and suggest Schottenol as a potential strategy to overcome breast cancer drug resistance.

论文信息

作者
Lu J、Ding F、Sun Y、Zhao Y、Ma W、Zhang H、Shi B
第一作者单位
Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong, China.; Department of Breast Diseases (II), Shandong Second Provincial General Hospital, Jinan 250000, Shandong, China.China
通讯作者单位
Department of Breast and Thyroid Surgery, The Qinghai Provincial People's Hospital, Xining 810007, China. Electronic address: profshibo@163.com.China
期刊
Cellular signalling2025 Mar
原文标识
PubMed 39818404 · DOI 10.1016/j.cellsig.2025.111608