Molecular Matchups

Study Identifies Key Molecules in Multiple Myeloma

Carlo CroceResearch led by scientists at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) links three molecules to a tumor-suppressor gene that is often turned off in multiple myeloma.

The silenced molecules – miR-192, miR-194 and miR-215 – are microRNAs, a class of molecules discovered about a decade ago that are master regulators of many cell processes. This study suggests that reactivating these three molecules triggers expression of the P53 tumor-suppressor gene, which in turn slows the growth and leads to the death of myeloma cells, possibly presenting a new strategy for treating this disease.

“Our findings provide a rationale for the further exploration of these microRNAs as a treatment for multiple myeloma, which has few therapeutic options,” says principal investigator Carlo Croce, MD, professor and chair of Molecular Virology, Immunology and Medical Genetics, and director of the Human Cancer Genetics Program.

Multiple myeloma begins as a benign condition called monoclonal gammopathy of undetermined significance (MGUS). Individuals with MGUS can live many years without treatment, but for unknown reasons this condition can evolve into myeloma. Studies have shown a relationship between P53 and a gene called MDM2. They have also shown that myeloma cells often have unmutated P53 genes but very little P53 protein. P53 protein levels are restored, however, when MDM2 expression is blocked.

Croce says the OSUCCC – James study, which examined the role of microRNA in regulating the P53 pathway in myeloma cells, provides the basis for developing a microRNA-based therapy for this disease.

Published in the journal Cell.

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