miR-301a promotes cell proliferation by directly targeting TIMP2 in multiple myeloma

摘要

Background: Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow and microRNAs play a crucial role in its tumorigenesis and development. The purpose of this study was to investigate the biological functions of miR-301a in MM. Methods: Quantitative real-time PCR was used to detect the expression level of miR-301a. Cell proliferation was assessed by MTT assay. Flow cytometry was performed to valuate cell apoptosis and cell cycle distribution. Moreover, luciferase reporter assay and western blot were conducted to determine the potential target of miR-301a in MM cells. Results: MiR-301a is significantly up-regulated in MM clinical bone marrow samples and cell lines compared with normal controls. Gain-of-function and loss-of-function studies in MM cell line U266 showed that miR-301a acts as an oncogene in MM by promoting cell proliferation and inhibiting apoptosis. Furthermore, a tumor suppressor gene, tissue inhibitor of metallopeptidases-2 (TIMP2) was identified as a direct target of miR-301a and knockdown of TIMP2 could mimic the effect of miR-301a in MM. Conclusions: MiR-301a promotes cell proliferation and inhibits apoptosis by direct targeting TIMP2 in MM, and miR-301a might represent a novel molecular in MM and may provide helpful therapeutic strategies for MM treatment.