Cancer Management and Research (Apr 2020)
MicroRNA-155 Suppresses the Translation of p38 and Impairs the Functioning of Dendritic Cells in Endometrial Cancer Mice
Abstract
Jianjun Jia,1 Xiaomao Li,2 Suiqun Guo,3 Xingmei Xie1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510632, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510632, People’s Republic of ChinaCorrespondence: Jianjun JiaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People’s Republic of ChinaTel/ Fax +86-020-38688359Email [email protected]: Dendritic cells (DCs) are reported to play an important role in activating the anti-tumor immune responses. p38 MAPK14 signaling plays an important role in controlling their activity. Here, we identified that miR-155 suppressed the translation of p38 and impaired the functioning of dendritic cells in endometrial cancer.Methods: HEC1A endometrial cancer cell lines were used for the study which was transfected in the C57BL/6 mice. Murine bone marrow-derived dendritic cells (BMDCs) were isolated from the mice. Target prediction was done by TargetScan which was confirmed by RT-PCR analysis. The protein expression was carried by Western blot analysis. Levels of IL-12 were evaluated by ELISA. Mice injected with HEC1A cells were subjected to tumor challenge study.Results: On screening the binding sites of p38 MAPK14 gene, miR-155 was found to bind the 3ʹUTR directly and blocked its translation. The levels of miR-155 were upregulated in dendritic cells and RAW264.7 cells, miR-155 showed inhibitory effect on expression levels of p38. In dendritic cells, miR-155 was found to regulate the expression of IL-12, also miR-155 inhibitor stimulated the differentiation of Th1 cells in mice induced with endometrial cancer. In dendritic cells, miR-155 inhibited the expression of p38 gene and decreased their ability to interfere in tumor growth.Conclusion: The study concludes suppressive role of miR-155 in the process of dendritic cells mediated anti-tumor immunity, also inhibiting miR-155 provides a novel strategy for countering endometrial cancer.Keywords: miR-155, dendritic cells, p38, IL-12, RAW264.7 cells
