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miRNA-21 抑制通过 PIAS3 和 STAT3 信号通路增强 MCF-7 中 RANTES 和 IP-10 的释放,并导致淋巴细胞迁移增加。

miRNA-21 inhibition enhances RANTES and IP-10 release in MCF-7 via PIAS3 and STAT3 signalling and causes increased lymphocyte migration.

机构信息

Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, Shandong, PR China; Shandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs, Ministry of Health, Shandong Academy of Medical Sciences, Jinan 250062, Shandong, PR China.

出版信息

Biochem Biophys Res Commun. 2013 Sep 27;439(3):384-9. doi: 10.1016/j.bbrc.2013.08.072. Epub 2013 Aug 30.

DOI:10.1016/j.bbrc.2013.08.072
PMID:23998932
Abstract

MicroRNAs (miRNAs) are a class of small endogenous gene regulators that have been implicated in various developmental and pathological processes. However, the precise identities and functions of miRNAs involved in antitumor immunity are not yet well understood. miRNA-21 is an oncogenic miRNA that can be detected in various tumours. In this study, we report that a miRNA-21 inhibitor enhances the release of chemoattractants RANTES and IP-10 in the MCF-7 breast cancer cell line and results in increased lymphocyte migration. Thus, miRNA-21 is a potential therapeutic target for cancer immunotherapy. We further demonstrated that PIAS3, a protein inhibitor of activated STAT3, is a target of miRNA-21 in MCF-7. Thus, miRNA-21 is a novel miRNA regulating immune cell recruitment, which acts at least in part via its inhibition of PIAS3 expression and oncogenic STAT3 signalling in tumour cells.

摘要

微小 RNA(miRNA)是一类内源性基因调控小 RNA,参与多种发育和病理过程。然而,miRNA 参与抗肿瘤免疫的确切身份和功能尚未完全了解。miRNA-21 是一种致癌 miRNA,可在各种肿瘤中检测到。在这项研究中,我们报告说,miRNA-21 抑制剂增强 MCF-7 乳腺癌细胞系中趋化因子 RANTES 和 IP-10 的释放,并导致淋巴细胞迁移增加。因此,miRNA-21 是癌症免疫治疗的潜在治疗靶点。我们进一步证明,PIAS3,一种激活 STAT3 的蛋白抑制剂,是 MCF-7 中 miRNA-21 的靶标。因此,miRNA-21 是一种新的 miRNA 调节免疫细胞募集,其至少部分通过抑制肿瘤细胞中 PIAS3 的表达和致癌 STAT3 信号传导来发挥作用。

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