Study Establishes Rationale for MicroRNA Treatment of Multiple Myeloma

Cancer researchers have found that inactivation of three microRNAs (miRNAs) in multiple myeloma (MM) cells permits the inhibition of the p53 tumor suppressor gene and stimulates the growth and spread of the cancer cells.

Multiple myeloma cells from patients show high expression of the p53 inhibitor MDM2 compared with MGUS (the benign condition monoclonal gammopathy of undetermined significance) cells and normal plasma cells. Furthermore, MM cells show reduced or absent activity of the miRNAs miR-192, miR-194, and miR-215.

Investigators at Ohio State University (Columbus, USA) sought to establish a relationship between the lack of microRNA expression and the enhanced activity of the p53 inhibitor.

They reported in the October 19, 2010, issue of the journal Cancer Cell that treating myeloma cells with the three microRNAs plus an MDM2 inhibitor caused a two-fold rise in P53 expression and a three-fold drop in MDM2 expression. Expression of miR-192, miR-194, and miR-215 in multiple myeloma cells slowed their growth and caused their death by activating the P53 gene.

Expression of the three microRNAs reduced the ability of myeloma cells to migrate and metastasize. Treating a myeloma mouse model with the three microRNAs caused a 50% reduction in tumor size compared with controls, while treating the mice with the microRNAs plus an MDM2 inhibitor brought a five-fold reduction in tumor size.

"These findings provide a rationale for the further exploration of these microRNAs as a treatment for multiple myeloma, which has few therapeutic options,” said senior author Dr. Carlo Croce, professor of molecular virology, immunology, and medical genetics at Ohio State University. "Overall our results provide the basis for developing a microRNA-based therapy for multiple myeloma.”

Related Links:
Ohio State University