Multiple tumor-associated microRNAs modulate the survival and longevity of dendritic cells by targeting YWHAZ and Bcl2 signaling pathways

Siping Min; Xue Liang; Miaomiao Zhang; Yuan Zhang; Shiyue Mei; Jinzhe Liu; Jingyi Liu; Xiaomin Su; Shuisong Cao; Xueqing Zhong; Yueming Li; Jiatan Sun; Qiaofei Liu; Xingran Jiang; Yongzhe Che; Rongcun Yang

doi:10.4049/jimmunol.1202282

Multiple tumor-associated microRNAs modulate the survival and longevity of dendritic cells by targeting YWHAZ and Bcl2 signaling pathways

J Immunol. 2013 Mar 1;190(5):2437-46. doi: 10.4049/jimmunol.1202282. Epub 2013 Jan 25.

Authors

Siping Min¹, Xue Liang, Miaomiao Zhang, Yuan Zhang, Shiyue Mei, Jinzhe Liu, Jingyi Liu, Xiaomin Su, Shuisong Cao, Xueqing Zhong, Yueming Li, Jiatan Sun, Qiaofei Liu, Xingran Jiang, Yongzhe Che, Rongcun Yang

Affiliation

¹ Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin 300071, China.

PMID: 23355742
DOI: 10.4049/jimmunol.1202282

Abstract

Tumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways. Specifically, miR-22 targeted YWHAZ to interrupt the PI3K/Akt and MAPK signaling pathways, and miR-503 downregulated Bcl2 expression. The result of the increased expression of miR-22 and miR-503 in the tumor-associated DCs was their reduced survival and longevity. Thus, tumor-associated miRNAs can target multiple intracellular signaling molecules to cause the apoptosis of DCs in the tumor environment. Use of miR-22 and miR-503 as inhibitors may therefore represent a new strategy to improve DC-based immunotherapies against tumors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

14-3-3 Proteins / genetics*
14-3-3 Proteins / immunology
Animals
Apoptosis / genetics
Apoptosis / immunology
Cell Line, Tumor
Cell Survival / genetics*
Cell Survival / immunology
Dendritic Cells / immunology
Dendritic Cells / metabolism*
Dendritic Cells / pathology
Female
Gene Expression Regulation
Humans
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
MicroRNAs / genetics
MicroRNAs / immunology
MicroRNAs / metabolism*
Mitogen-Activated Protein Kinases / genetics
Mitogen-Activated Protein Kinases / immunology
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / immunology
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / immunology
Proto-Oncogene Proteins c-bcl-2 / genetics*
Proto-Oncogene Proteins c-bcl-2 / immunology
RNA, Small Interfering / genetics
Signal Transduction / immunology*
Transfection

Substances

14-3-3 Proteins
MicroRNAs
Proto-Oncogene Proteins c-bcl-2
RNA, Small Interfering
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinases