MiR-29 MicroRNAs Regulate IGF-1R Expression and Contribute Mantle Cell Lymphoma Growth and Survival.

Abstract 1957

Poster Board I-980

Mantle cell lymphoma (MCL) is now recognized as a distinct clinicopathologic subtype of B-cell lymphomas and carries the poorest prognosis among NHL subtypes with a median survival is 3 to 4 years. Clearly better understanding of MCL oncogenesis and novel therapeutic approaches to treating MCL are needed. Mounting evidence now shows that small noncoding microRNAs (miRNAs) can play roles as oncogenes or tumor suppressor genes, suggesting their contribution to cancer development and progression. Here, we for the first time, demonstrated that that miR-29a-c is frequently deleted or down-regulated and IGF-1R is often over-expressed in primary mantle cell lymphoma cells. Expression of miR-29 inversely correlates with the expression of IGF-1R. Consistent with these results, 1) overexpression of miR-29-c down-regulated IGF-R1, 2) overexpression of miR-29c inhibited cell growth, colony formation and induced cell cycle arrest in MCL cells, 3) depletion of miR-29-c by anti-miR29-c increased the threshold for apoptosis, 4) enforced expression of miR-29c suppressed MCL growth and tumor progression in NOD/SCID mouse xenograft models, 5) miR-29 directly regulates IGF-1R expression . Furthermore cell cycle arrest induced by these miRNAs depends on the expression of IGF-1R. Our results indicate that miR-29a-c are implicated in MCL cell cycle control, survival and likely contribute to the tumorigenesis of MCL.