Long intergenic non-protein coding RNA 152 promotes multiple myeloma progression by negatively regulating microRNA-497

摘要

Long intergenic non-protein coding RNA 152 (LINC00152, also known as cytoskeleton regulator RNA) is reportedly involved in the development and progression of various types of human malignancy. However, the functional role of LINC00152 in multiple myeloma (MM) and the underlying molecular mechanisms have remained elusive. The present study aimed to investigate the role of LINC00152 in the genesis of MM and the potential molecular mechanisms. It was identified that the expression of LINC00152 was significantly upregulated in plasma cells from patients with MM vs. healthy subjects, and that a high expression of LINC00152 was correlated with a shorter overall survival in patients with MM. Functional assays demonstrated that knockdown of LINC00152 by transfecting MM cells with LINC00152-specific short hairpin RNA expression plasmids significantly inhibited cell proliferation by inducing cell cycle arrest at the G(0)/G(1) phase. Furthermore, knockdown of LINC00152 promoted caspase-3/9 activity and apoptosis in MM cells. In addition, knockdown of LINC00152 significantly attenuated tumor growth in mice bearing a myeloma xenograft. A luciferase reporter assay indicated that microRNA (miR)-497 is a direct target of LINC00152, and its expression levels were inversely correlated with those of LINC00152 in MM tissues. Furthermore, repression of miR-497 partly abrogated the inhibitory effects of LINC00152 knockdown on MM cells. Collectively, the results indicated that LINC00152 has an oncogenic effect in MM by targeting miR-497, and may be a novel diagnostic marker and therapeutic target for MM.