MicroRNA-497 inhibits multiple myeloma growth and increases susceptibility to bortezomib by targeting Bcl-2

Abstract

Multiple myeloma (MM) is a common severe hematopoietic malignancy occuring in aged population. MicroRNA (miR)-497 was previously reported to contribute to the apoptosis of other cell types, presumably through targeting B-cell lymphoma 2 (Bcl-2). In the present study, miRNA and protein expression levels were detected by reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The cell proliferation and viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and plate clonality assays, and the cell growth cycle was measured with a flow cytometer. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling, Annexin V and caspase-3 activity assays were performed to examine the cell apoptotic rates. The results showed that miR-497 was markedly decreased, whereas Bcl-2 was enhanced in MM tissues and cell lines. miR-497 targeted Bcl-2 and affected its downstream apoptosis-related genes. The overexpression of miR-497 promoted MM cell apoptosis through cell cycle arrest, and decreased colony genesis ability and viability. In addition, miR-497 increased the sensitivity of MM cells to bortezomib. Taken together, miR-497 suppressed MM cell proliferation and promoted apoptosis by directly targeting Bcl-2 and altering the expression of downstream apoptosis-related proteins. The combination of miR-497 and bortezomib may enhance drug sensitivity, serving as a potentially available therapeutic method for MM.