The Pseudogene Olfr29-ps1 Promotes the Suppressive Function and Differentiation of Monocytic MDSCs

Long noncoding RNA (lncRNA) plays a critical role in many biological processes, such as cell differentiation and development. However, few studies about lncRNAs regulating the differentiation and development of myeloid-derived suppressor cells (MDSCs) exist. In this study, we identified a lncRNA pseudogene, Olfr29-ps1, which was expressed in MDSCs and upregulated by the proinflammatory cytokine IL6. The Olfr29-ps1 in vertebrates is conserved, and the similarity between the Olfr29-ps1 and human OR1F2P sequence is 43%. This lncRNA promoted the immunosuppressive function and differentiation of monocytic (Mo-)MDSCs in vitro and in vivo. It directly sponged miR-214-3p to downregulate miR-214-3p, which may target MyD88 to modulate the differentiation and development of MDSCs. The functions of Olfr29-ps1 were dependent on IL6-mediated N-6-methyladenosine (m6A) modification, which not only enhanced Olfr29-ps1, but also promoted the interaction of Olfr29-ps1 with miR-214-3p. Thus, our results demonstrated that the pseudogene Olfr29-ps1 may regulate the differentiation and function of MDSCs through a m6A-modified Olfr29-ps1/miR-214-3p/MyD88 regulatory network, revealing a mechanism for the regulation of myeloid cells and also providing potential targets for antitumor immunotherapy.