title: MicroRNA-155 deficiency enhances the recruitment and functions of myeloid-derived suppressor cells in tumor microenvironment and promotes solid tumor growth.
abstract: Immune cells in tumor microenvironment play a prominent role in tumor progression and metastasis. MicroRNA-155 (miR-155) represents an important player in innate and adaptive immunity by regulating differentiation, maturation and activation of macrophages, dendritic cells, B cells and T cells. However, the role of miR-155 expression in immune cells in solid tumor development is less elucidated. Our current study showed that both B16-F10 melanoma and Lewis lung carcinoma tumors grew much faster in bic/miR-155 knockout (miR-155(-/-) ) mice along with an increase of myeloid-derived suppressor cells (MDSCs) accumulation in tumors, compared to that in wild-type mice. Bone marrow transplantation study showed that bone marrow miR-155 deficiency could replicate the above tumor-promoting phenotype. In vitro study demonstrated that tumor-infiltrating miR-155(-/-) MDSCs showed greater migration ability and expressed higher level of multiple chemokines. Furthermore, we found that the level of HIF-1α, a direct target of miR-155, was increased in miR-155 deficient MDSCs, and that the increased HIF-1α upregulated CXCL1, CXCL3 and CXCL8 expression in MDSCs, contributing to the enhanced recruitment of miR-155(-/-) MDSCs to the tumors. Moreover, miR-155(-/-) MDSCs showed enhanced immunosuppressive and pro-angiogenic capacities. Taken together, our study, for the first time, demonstrated that miR-155 deficiency promoted solid tumor growth through increasing the recruitment of MDSCs to tumor microenvironment and enhancing the tumor-promoting functions of the recruited MDSCs. Thus, upregulating miR-155 expression in MDSCs may be developed as a therapeutic approach to halt tumor development.
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, 29209; Centre for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Jia
authors.forename: Stephen
authors.initials: S
authors.lastname: Iwanowycz
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wang
authors.forename: Shiang
authors.initials: S
authors.lastname: Huang
authors.forename: Walden
authors.initials: W
authors.lastname: Ai
authors.forename: Daping
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D022423:Myeloid Cells / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse
keywords: HIF-1α; MDSCs; chemokines; microRNA-155; tumor growth