Restoration of microRNA-373 suppresses growth of human T-cell lymphoma cells by repressing CCND1.

ABSTRACT

OBJECTIVE: Adult T cell lymphoma is a highly aggressive T-cell malignancy. This study was designed to explore the expression and functional significance of microRNA (miR)-373 in T cell lymphoma. PATIENTS AND METHODS: We analyzed the levels of CCND1 and miR-373 in T cell lymphoma tissue and the relationship of miR-373 levels with patients' prognosis. We then overexpressed miR-373 by miRNA mimics transfection and inhibited miR-373 by miRNA antisense transfection in T cell lymphoma cells. Cell survival and growth were analyzed by CCK-8 assay and MTT assay, respectively. Cell proliferation was analyzed by flow cytometry. Bioinformatics analyses were applied to predict miR-373 targets, which were then confirmed by luciferase reporter assay. RESULTS: We detected significantly higher levels of CCND1, and significantly lower levels of miR-373 in T cell lymphoma tissue, compared to the adjacent non-tumor tissue. Moreover, the low miR-373 levels were associated with poor survival of the patients. Overexpression of miR-373 significantly inhibited cell growth, while depletion of miR-373 increased cell growth in T cell lymphoma cells. Moreover, the effects of miR-373 on cell growth appeared to result from an alteration in cell proliferation. Finally, miR-373 was found to bind to the 3'-UTR of CCND1 mRNA to inhibit its translation in T cell lymphoma cells. CONCLUSIONS: Our study suggests that reduced miR-373 levels in T cell lymphoma tissue may promote T cell lymphoma growth, possibly through CCND1-mediated cell proliferation.