LncRNA RNCR3 promotes Chop expression by sponging miR-185-5p during MDSC differentiation

Oncotarget. 2017 Dec 4;8(67):111754-111769. doi: 10.18632/oncotarget.22906. eCollection 2017 Dec 19.


Myeloid-derived suppressor cells (MDSCs) play a critical role in regulating immune responses in cancer and other pathological conditions. Mechanism(s) regulating MDSC differentiation and function is not completely clear, especially epigenetic regulation. In this study, we found that MDSCs express retinal non-coding RNA3 (RNCR3), and the expression in MDSCs is upregulated by inflammatory and tumor associated factors. RNCR3 may function as a competing endogenous RNA (ceRNA) to promote Chop expression by sponging miR-185-5p during MDSC differentiation. RNCR3 knockdown suppressed differentiation and function of MDSCs in vitro and in vivo. Quantitative RT-PCR showed that RNCR3 was negatively regulated by miR-185-5p in MDSCs. MiR-185-5p affected the expansion of MDSCs and reversed the effect of RNCR3 on MDSC differentiation and function through directly targeting Chop. Thus, our results suggest a RNCR3/miR-185-5p/Chop autologously strengthening network to promote MDSC differentiation and suppressive function in response to extracellular inflammatory and tumor-associated signals.

Keywords: Chop; RNCR3; epigenetic modification; miR-185-5p; myeloid-derived suppressor cells.