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Biochem Biophys Res Commun. 2009 Oct 23;388(3):483-9. doi: 10.1016/j.bbrc.2009.07.143. Epub 2009 Aug 3.

MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer.

Author information

1
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, DHLRI, 473 West 12th Avenue, Room 201, Columbus, OH 43210, USA.

Abstract

Lung cancer is the most frequent cause of cancer-related death in this country for men and women. MicroRNAs (miRNAs) are a family of small non-coding RNAs (approximately 21-25nt long) capable of targeting genes for either degradation of mRNA or inhibition of translation. We identified aberrant expression of 41 miRNAs in lung tumor versus uninvolved tissue. MiR-133B had the lowest expression of miRNA in lung tumor tissue (28-fold reduction) compared to adjacent uninvolved tissue. We identified two members of the BCL-2 family of pro-survival molecules (MCL-1 and BCL2L2 (BCLw)) as predicted targets of miR-133B. Selective over-expression of miR-133B in adenocarcinoma (H2009) cell lines resulted in reduced expression of both MCL-1 and BCL2L2. We then confirmed that miR-133B directly targets the 3'UTRs of both MCL-1 and BCL2L2. Lastly, over-expression of miR-133B induced apoptosis following gemcitabine exposure in these tumor cells. To our knowledge, this represents the first observation of decreased expression of miR-133B in lung cancer and that it functionally targets members of the BCL-2 family.

PMID:
19654003
PMCID:
PMC2824514
DOI:
10.1016/j.bbrc.2009.07.143
[Indexed for MEDLINE]
Free PMC Article

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