Effects of the miR-143/-145 MicroRNA Cluster on the Colon Cancer Proteome and Transcriptome

The miR-143/-145 cluster is greatly reduced in several
cancers,
including colon cancer. Both miR-143 and miR-145 have been shown to
possess antitumorigenic activity with involvement in various cancer-related
events such as proliferation, invasion, and migration. As the deregulation
of the miR-143/-145 cluster is implicated in tumorigenesis, we combined
SILAC and microarray analyses to systematically interrogate the impact
of miR-143/-145 on the colon cancer proteome and transcriptome. Using
SILAC, we identified over 2000 proteins after reintroduction of miR-143
and miR-145, in the colon cancer cell line SW480, individually, and
then, in concert. Our goal was to determine whether these microRNAs
function individually or synergistically. The resulting regulated
gene products showed evidence of both mRNA destabilization and translational
inhibition with a bias toward the former mechanism of regulation.
Numerous candidate targets were identified whose expression is attributable
to an individual microRNA or whose regulation was more apparent following
reintroduction of the miR-143/-145 cluster. In addition, several shared
targets of miR-143 and miR-145 were identified. Overall, our results
indicate that the summed effects of individually introduced microRNAs
produce distinct molecular changes from the consequences of the assembled
cluster. We conclude that there is a need to investigate both the
individual and combined functional implications of a microRNA cluster.