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miRNA-21 inhibition enhances RANTES and IP-10 release in MCF-7 via PIAS3 and STAT3 signalling and causes increased lymphocyte migration
Authors:Zhiyu Wang  Jinxiang Han  Yazhou Cui  Xiaoyan Zhou  Kaixi Fan
Institution:1. Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, Shandong, PR China;2. Shandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs, Ministry of Health, Shandong Academy of Medical Sciences, Jinan 250062, Shandong, PR China;3. Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan 250031, Shandong, PR China
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.
Keywords:Cancer immunotherapy  Immunoresistance  Chemokine  microRNA  PIAS3  STAT3
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