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

Journal Article · Fri Mar 25 04:00:00 EDT 2011 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.02.065· OSTI ID:22204847

Park, Jong-Kook ^[1]; Henry, Jon C. ^[2]; Jiang, Jinmai ^[1]; Esau, Christine ^[3]; Gusev, Yuriy ^[4]; Lerner, Megan R. ^[5]; Postier, Russell G. ^[6]; Brackett, Daniel J. ^[5]

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1. College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States)
2. Department of Surgery, Ohio State University, Columbus, OH 43210 (United States)
3. Regulus Therapeutics, Carlsbad, CA (United States)
4. Lombardi Cancer Center, Georgetown University, Washington, DC (United States)
5. Veterans Affairs Medical Center, Oklahoma City, OK (United States)
6. Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

Research highlights: {yields} The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. {yields} miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. {yields} miR-132 and miR-212 expression is increased by a {beta}2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- 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{sub 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 {beta}2 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 {beta}2 adrenergic pathway may play an important role in this novel mechanism.

• OSTI ID: 22204847
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 406; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
CARCINOMAS
CELL CYCLE
CELL PROLIFERATION
CHROMOSOMES
GENES
LUCIFERASE
MESSENGER-RNA
PANCREAS
RECEPTORS