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调控异常的 microRNAs 参与乳腺癌 P53 信号通路,重点关注三阴性乳腺癌。

Deregulated MicroRNAs involved in P53 Signaling Pathway in Breast Cancer with Focus on Triple-negative Breast Cancer.

机构信息

Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.

Bone and Joint Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Curr Mol Pharmacol. 2024;17(1):e18761429263841. doi: 10.2174/0118761429263841230926014118.

Abstract

BACKGROUND

Breast cancer (BC), as a heterogenous disease, is the most common cancer among women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive and malignant subtype with a poor prognosis and a high rate of relapse and metastasis that is closely linked to epithelial-mesenchymal transition (EMT). It is well-documented that miRNAs play oncogenic (oncomiR) or tumor-suppressive (TS-miR) roles in controlling apoptosis (apoptomiR), differentiation, cell proliferation, invasion, migration, etc. Regarding the regulatory roles of miRNAs in the expression levels of various genes, dysfunction or deregulated expression of these molecules can lead to various disorders, including various types of cancers, such as BC. Many miRNAs have been identified with critical contributions in the initiation and development of different types of BCs due to their influence on the p53 signaling network.

OBJECTIVE

The aim of this review was to discuss several important deregulated miRNAs that are involved in the p53 signaling pathway in BC, especially the TNBC subtype. Finally, miRNAs' involvement in tumor properties and their applications as diagnostic, prognostic, and therapeutic agents have been elaborated in detail.

RESULTS

The miRNA expression profile of BC is involved in tumor-grade estrogen receptor (ER) and progesterone receptor (PR) expression, and other pathological properties from luminal A to TNBC/basal-like subtypes via p53 signaling pathways.

CONCLUSION

Developing our knowledge about miRNA expression profile in BC, as well as molecular mechanisms of initiation and progression of BC can help to find new prognostic, diagnostic, and therapeutic biomarkers, which can lead to a suitable treatment for BC patients.

摘要

背景

乳腺癌(BC)作为一种异质性疾病,是全球女性中最常见的癌症。三阴性乳腺癌(TNBC)是最具侵袭性和恶性的亚型,预后不良,复发和转移率高,与上皮-间充质转化(EMT)密切相关。有充分的证据表明,miRNA 在控制细胞凋亡(凋亡 miRNA)、分化、细胞增殖、侵袭、迁移等方面发挥致癌(oncomiR)或肿瘤抑制(TS-miR)作用。关于 miRNA 对各种基因表达水平的调控作用,这些分子的功能障碍或失调表达可导致各种疾病,包括各种类型的癌症,如 BC。由于 miRNA 对 p53 信号网络的影响,许多 miRNA 已被确定在不同类型 BC 的发生和发展中具有重要作用。

目的

本综述的目的是讨论参与 BC 中 p53 信号通路的几种重要失调 miRNA,特别是 TNBC 亚型。最后,详细阐述了 miRNA 参与肿瘤特性及其作为诊断、预后和治疗剂的应用。

结果

BC 的 miRNA 表达谱通过 p53 信号通路参与肿瘤分级、雌激素受体(ER)和孕激素受体(PR)表达以及从 luminal A 到 TNBC/基底样亚型的其他病理特性。

结论

深入了解 BC 中 miRNA 表达谱以及 BC 发生和进展的分子机制,有助于寻找新的预后、诊断和治疗生物标志物,从而为 BC 患者提供合适的治疗方法。

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