Ribophorin II is upregulated in myelodysplastic syndromes and prevents apoptosis and cell cycle progression

Abstract

Myelodysplastic syndromes (MDSs) are a series of heterogeneous diseases affecting hematopoietic stem cells that result in hematopoiesis disturbance and leukemic transformation. As an essential cell cycle regulator, ribophorin II (RPN2) has been extensively identified as a prospective predictor of prognosis in diverse malignant tumors. However, its effects on MDS are unclear. We observed increased mRNA expression RPN2 in samples from MDS patients, compared with samples from normal healthy controls. RPN2 overexpression promoted the proliferation of Ontario Cancer Institute OCI-acute myeloid leukemia 3 (OCI-AML3) cells, whereas RPN2 silencing clearly suppressed the proliferation of OCI-AML3 cells. Furthermore, RPN2 silencing caused G1/S cell cycle arrest and cell apoptosis. In addition, RPN2 overexpression led to a higher proportion of cells in the G2/M phase and reduced cell apoptosis. RPN2 overexpression downregulated enhancer of zeste homolog-2 (EZH2) expression, whereas RPN2 downregulation increased EZH2 expression in a dose-dependent manner. Co-immunoprecipitation showed an interaction between RPN2 and EZH2. Additionally, the administration of 3-deazaneplanocin A, an EZH2 inhibitor, reversed the function of RPN2 silencing in cell cycle arrest and apoptosis induction in OCI-AML3 cells. Hence, RPN2 is an essential regulator of cell proliferation. This study described the etiology of OCI-AML3 cell proliferation regulated by RPN2 and EZH2. Impact statement This study explored the role of ribophorin II (RPN2) in myelodysplastic syndromes (MDSs) cell proliferation and growth and revealed that RPN2 knockdown suppressed OCI-AML3 cell growth and proliferation and triggered cell cycle arrest and elicited apoptosis in OCI-AML3 cells. In addition, it shed light on the etiology of RPN2’s role in MDS cell proliferation that RPN2 can negatively impact enhancer of zeste homolog-2 (EZH2) expression, which in turn is able to modulate the cell cycle location and death in OCI-AML3 cells. Hence, RPN2 expression could be a latent predictor of prognosis in patients with MDS.