A microRNA signature of hypoxia.
Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these noncoding transcripts. Here, we demonstrate for the first time a functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression. Microarray-based expression profiles revealed that a specific spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210, and -213) is induced in response to low oxygen, at least some via a hypoxia-inducible-factor-dependent mechanism. Select members of this group (miR-26, -107, and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation. Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.
Kulshreshtha
Ritu
R
Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
Ferracin
Manuela
M
Wojcik
Sylwia E
SE
Garzon
Ramiro
R
Alder
Hansjuerg
H
Agosto-Perez
Francisco J
FJ
Davuluri
Ramana
R
Liu
Chang-Gong
CG
Croce
Carlo M
CM
Negrini
Massimo
M
Calin
George A
GA
Ivan
Mircea
M
D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D035683:MicroRNAs; D008156:Luciferases