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Biochem Biophys Res Commun. 2011 Mar 25;406(4):518-23. doi: 10.1016/j.bbrc.2011.02.065. Epub 2011 Feb 15.

miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor.

Author information

1
College of Pharmacy, Ohio State University, Columbus, OH 43210, United States.

Abstract

Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G(2)/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the β2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The β2 adrenergic pathway may play an important role in this novel mechanism.

PMID:
21329664
PMCID:
PMC3069485
DOI:
10.1016/j.bbrc.2011.02.065
[Indexed for MEDLINE]
Free PMC Article

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