acts as a tumor suppressor by negatively regulating the cluster.

Anaplastic thyroid cancer (ATC) is an aggressive, highly metastatic cancer that expresses high levels of the microRNA ( cluster. We employ an miR inhibitor system to study the function of the different miRs within the cluster based on seed sequence homology in the ATC SW579 cell line. While three of the four families were oncogenic, we uncovered a novel role for as a tumor suppressor and . Surprisingly, inhibition increased expression of the cluster and significantly increased the levels of the and mature miRs. inhibition increased expression of the cell cycle activator CCND2, associated with increased cell proliferation and tumor growth in transplanted SW579 cells in xenograft mice. regulates and expression in SW579 cells, and the inhibition of increased and expression, which increased transcripts. Thus, inhibition of activated the expression of the oncogenic miRs, and . While many cancers express high levels of , linking it with tumorigenesis, we demonstrate that inhibition does not inhibit thyroid tumor growth in SW579 and MDA-T32 ATC cells but increases expression of the other family members and genes to induce cancer progression.