Prominent role of RAB39A-RXRB axis in cancer development and stemness.

In this study, we found that , a member of the RAS oncogene family, was selectively expressed in cancer cells of different histotypes, by analyzing gene expression in human osteosarcoma cells and the cancer stem cells (CSCs) and by comparing them with normal cells through global transcriptomics and principal component analyses. We further validated as a therapeutic target, by silencing its expression. The silencing impaired cancer stemness and spherogenic ability , as well as tumorigenesis . RNA-seq analyses in the silenced spheres suggested that RAB39A is associated downstream with RXRB and KLF4. Notably, expression was inhibited in -silenced CSCs. Induced overexpression of in -silenced cells restored spherogenic ability and tumorigenesis, confirming RXRB as a major effector of RAB39A. Quantitative RT-PCR analysis of ∼400 human cancer tissues showed that was highly expressed in sarcomas and in malignancies of lymphoid, adrenal and testicular tissues. Our data provide the rationale for targeting of the RAB39A-RXRB axis as a therapy for aggressive cancers.