Dataset Information

Effects of the miR-143/-145 microRNA cluster on the colon cancer proteome and transcriptome.

ABSTRACT: 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.

SUBMITTER: Bauer KM

PROVIDER: S-EPMC3446753 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Effects of the miR-143/-145 microRNA cluster on the colon cancer proteome and transcriptome.

Bauer Kerry M KM Hummon Amanda B AB

Journal of proteome research 20120827 9

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 SILA ...[more]

PMID: 22897626

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Project description:MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression and are dysregulated in cancer. Studies of miRNAs to explore their potential as diagnostic and prognostic markers are of great scientific interest. Here, we investigate the functional properties and expression of the miR-143/145 cluster in breast cancer (BC) in vitro and in vivo. The ER positive MCF7, the HER2 positive SK-BR-3, and the triple negative cell line MDA-MB-231 were used to assess cell proliferation and cell invasion. Expression of miRNA in 108 breast cancers in the Norwegian Women and Cancer Study and 44 benign tissue controls were analyzed by microarray and validated by RT-PCR. Further, in situ hybridization (ISH) was used to study the cellular and subcellular distribution of the miRNAs. In vitro, miR-143 promoted proliferation of MCF7 and MDA-MB-231 cells, whereas miR-145 and the cotransfection of both miRNAs inhibited proliferation in all three cell lines. The cells' invasive capacity was reduced after transfection and cotransfection of the miRNAs. In line with the tumor suppressive functions in vitro, the expression of miR-143 and miR-145 was lower in malignant compared to benign breast tissue, and lower in the more aggressive tumors with higher tumor grade, loss of ER and the basal-like phenotype. ISH revealed miR-143 to be cytoplasmatic and predominantly expressed in luminal cells in benign tissue, whilst miR-145 was nuclear and with strong staining in myoepithelial cells. Both miRNAs were present in malignant epithelial cells and stromal fibroblasts in BC. This study demonstrates that miR-143 and -145 have functional properties and expression patterns typical for tumor suppressors, but the function is influenced by cellular factors such as cell type and miRNA cotransfection. Further, the nuclear functions of miR-145 should be explored for a more complete understanding of the complexity of miRNA regulation and function in BC.

Dataset Information

Effects of the miR-143/-145 microRNA cluster on the colon cancer proteome and transcriptome.

Publications

Effects of the miR-143/-145 microRNA cluster on the colon cancer proteome and transcriptome.

Similar Datasets

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