外泌体 miR-423-3p 抑制巨噬细胞 M2 极化以抑制宫颈癌的恶性进展。
Exosomal MiR-423-3p inhibits macrophage M2 polarization to suppress the malignant progression of cervical cancer.
机构信息
The Drug Clinical Trial Institution, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Department of Gynecology, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China.
出版信息
Pathol Res Pract. 2022 Jul;235:153882. doi: 10.1016/j.prp.2022.153882. Epub 2022 Apr 6.
BACKGROUND
Cervical cancer (CC) is the leading cause of death among women-related cancers. MicroRNAs (miRNAs) exerting important impacts in the development of CC is widely recognized. MiR-423-3p was found to be with low expression in the plasma exosomes of patients with CC. Exo-miRNAs have been documented to be potential modulators of cancer progression, and exosomes have been reported to be associated with macrophage polarization.
AIM
We aim to verify the potential function exosomal miR-423-3p may exert in CC cells as well as its underlying mechanism.
METHODS
A co-culture model of exosomes and CC cells was established and the function of exosomal miR-423-3p was verified through Transwell, colony formation and other assays. A co-culture model of exosomes and macrophages, together with mechanism experiments in vitro and in vivo was taken to verify the molecular mechanism of exosomal miR-423-3p in CC.
RESULTS
Exosomal miR-423-3p inhibited macrophage M2 polarization so as to suppress CC cell progression as well as tumor growth. MiR-423-3p regulated macrophage M2 polarization by targeting cyclin-dependent kinase 4 (CDK4) mRNA, and it inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) via CDK4 to silence Interleukin 6 (IL-6) expression.
CONCLUSION
Exosomal miR-423-3p inhibited macrophage M2 polarization to suppress the progression of CC cells.
背景
宫颈癌（CC）是女性癌症相关死亡的主要原因。人们广泛认识到，microRNAs（miRNAs）在 CC 的发展中发挥着重要作用。研究发现，CC 患者血浆外泌体中的 miR-423-3p 表达水平较低。外泌体 miRNAs 已被证明是癌症进展的潜在调节剂，并且已有报道称外泌体与巨噬细胞极化有关。
目的
我们旨在验证外泌体 miR-423-3p 在 CC 细胞中可能发挥的潜在功能及其潜在机制。
方法
建立了外泌体和 CC 细胞的共培养模型，并通过 Transwell、集落形成等实验验证了外泌体 miR-423-3p 的功能。通过外泌体和巨噬细胞的共培养模型以及体外和体内的机制实验，验证了外泌体 miR-423-3p 在 CC 中的分子机制。
结果
外泌体 miR-423-3p 抑制巨噬细胞 M2 极化，从而抑制 CC 细胞的进展和肿瘤生长。miR-423-3p 通过靶向细胞周期蛋白依赖性激酶 4（CDK4）mRNA 调节巨噬细胞 M2 极化，并通过 CDK4 抑制信号转导和转录激活因子 3（STAT3）的磷酸化，从而沉默白细胞介素 6（IL-6）的表达。
结论
外泌体 miR-423-3p 抑制巨噬细胞 M2 极化，从而抑制 CC 细胞的进展。
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