title: miRNA-21 inhibition enhances RANTES and IP-10 release in MCF-7 via PIAS3 and STAT3 signalling and causes increased lymphocyte migration.
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.
authors.affiliation: 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.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Wang
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Han
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Cui
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.forename: Kaixi
authors.initials: K
authors.lastname: Fan
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018946:Chemokine CCL5 / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D018832:Molecular Chaperones / Q000235:genetics / Q000276:immunology*; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000276:immunology*; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction
chemical_list: C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones; C484745:PIAS3 protein, human; D050828:Protein Inhibitors of Activated STAT; D050796:STAT3 Transcription Factor
keywords: Cancer immunotherapy; Chemokine; Immunoresistance; PIAS3; STAT3; microRNA