Wang CC, et al. Eur Rev Med Pharmacol Sci 2020.
OBJECTIVE: This study aims to clarify the influences of miRNA-584 on proliferative and invasive abilities in NK/T-cell lymphoma, and to illustrate the underlying mechanism.
PATIENTS AND METHODS: MiRNA-584 levels in peripheral blood of NK/T-cell lymphoma patients and healthy controls were detected by qRT-PCR. Potential relationship between miRNA-584 level and clinical indicators of NK/T-cell lymphoma patients was analyzed. Kaplan-Meier curves were depicted for assessing the prognostic value of miRNA-584 in NK/T-cell lymphoma patients. After overexpression or knockdown of miRNA-584, changes in proliferative and invasive abilities in KHYG-1 and SNK-6 cells were assessed by CCK-8 and transwell assay, respectively. The potential mechanism of miRNA-584 and its downstream gene FOXO1 in regulating the development of NK/T-cell lymphoma was explored by Dual-Luciferase reporter gene assay and rescue experiments.
RESULTS: Peripheral blood levels of miRNA-584 were lower in NK/T-cell lymphoma patients than those of healthy control. Compared with NK/T-cell lymphoma patients expressing high level of miRNA-584, those expressing a low level suffered worse tumor staging, higher rate of bone marrow invasion, and worse prognosis. Overexpression of miRNA-584 suppressed proliferative and invasive abilities in KHYG-1 and SNK-6 cells. On the contrary, knockdown of miRNA-584 yielded the opposite results. FOXO1 was showed to be the direct target binding miRNA-584, and its level was negatively regulated by miRNA-584. Notably, FOXO1 could partially abolish the regulatory effects of miRNA-584 on proliferative and invasive abilities in NK/T-cell lymphoma.
CONCLUSIONS: Low level of miRNA-584 is closely linked to advanced stage, susceptibility to bone marrow invasion, and poor prognosis in NK/T-cell lymphoma. MiRNA-584 suppresses proliferative and invasive abilities in NK/T-cell lymphoma by targeting FOXO1.