ATPR regulates human mantle cell lymphoma cells differentiation via SOX11/CyclinD1/Rb/E2F1.

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder that lacks reliable therapeutic options. Therefore, new treatment approaches for targeting novel biological pathways are required. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) synthesized by our group previously has been proven to have higher solubility and superior differentiation effects compared to those of conventional all-trans retinoic acid in acute myeloid leukemia. ATPR induces differentiation and inhibits the proliferation of acute promyelocytic leukemia. However, whether ATPR induces differentiation of MCL cells to normal immune cells has not been investigated. In this study, the proliferation of JEKO-1 cells was completely repressed, and differentiation was activated after ATPR treatment. The neural transcription factor SOX11 was further found to be highly expressed in MCL, but was downregulated by ATPR. After silencing SOX11 in vitro and in vivo, the malignant proliferation and inhibited differentiation of JEKO-1 cells were reversed, whereas the overexpression of SOX11 exacerbated the malignant phenotype of JEKO-1 cells. We also have added additional MCL cell lines (MINO) to complete the key pilot experiments. In addition, the CyclinD1/Rb/E2F1 axis was involved in MCL and was regulated by ATPR. In conclusion, ATPR promoted JEKO-1 cell differentiation via SOX11/CyclinD1/Rb/E2F1. This study provides experimental foundation for developing differentiation therapy for MCL with ATPR.