MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines.
BACKGROUND
MicroRNAs (miRNAs) are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis.


RESULTS
Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6.


CONCLUSIONS
We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors.
Takahashi
Yukari
Y
RNA Function Research Team, Omics Science Center, RIKEN Yokohama Institute, Yokohama, Japan.
Forrest
Alistair R R
AR
Maeno
Emi
E
Hashimoto
Takehiro
T
Daub
Carsten O
CO
Yasuda
Jun
J
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs
J Cell Biol. 2009 Jan 12;184(1):67-82
19139263
Cancer Res. 2007 Sep 15;67(18):8433-8
17823410
Cell Cycle. 2007 Sep 1;6(17):2127-32
17786041
Nature. 2005 Jun 9;435(7043):828-33
15944707
Mol Cell. 2007 Jun 8;26(5):745-52
17540599
Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15472-7
17875987
Nat Rev Cancer. 2007 Nov;7(11):819-22
17914404
Oncogene. 2007 Oct 4;26(45):6488-98
17471240
Curr Biol. 2007 Aug 7;17(15):1298-307
17656095
Trends Biochem Sci. 2008 Oct;33(10):474-81
18774719
Cancer Res. 2008 Jan 1;68(1):26-33
18172293
Cell. 2003 Dec 26;115(7):787-98
14697198
Nature. 2007 Jun 28;447(7148):1130-4
17554337
Mol Cell. 2004 Dec 22;16(6):861-5
15610730
J Clin Oncol. 2006 Oct 10;24(29):4677-84
16966691
Nat Genet. 2005 May;37(5):495-500
15806104
Cancer Res. 2003 Jul 1;63(13):3593-7
12839946
Bioinformatics. 2004 Jun 12;20(9):1464-5
14962934
Nat Rev Genet. 2004 May;5(5):396-400
15143321
Mol Cell Biol. 2007 Mar;27(6):2240-52
17242205
Mol Cancer. 2006 Jul 19;5:29
16854228
Mol Genet Metab. 2007 Jul;91(3):209-17
17521938
Nature. 2000 Nov 2;408(6808):86-9
11081512
Cancer Res. 2004 Jun 1;64(11):3753-6
15172979
Urol Oncol. 2007 Sep-Oct;25(5):387-92
17826655
Mamm Genome. 2000 Sep;11(9):718-24
10967128
PLoS One. 2009;4(5):e5610
19440340
Cancer Res. 2007 Aug 15;67(16):7713-22
17699775
Mol Cell. 2007 Jun 8;26(5):731-43
17540598
Nature. 2005 Jun 9;435(7043):839-43
15944709
Nucleic Acids Res. 2005 Mar 01;33(4):1290-7
15741182
Adv Cancer Res. 2008;99:77-112
18037407
Cancer Res. 2005 Jul 1;65(13):5561-70
15994928
C R Biol. 2003 Oct-Nov;326(10-11):1079-82
14744116
Cell. 2008 Jan 11;132(1):9-14
18191211
Exp Hematol. 2007 Apr;35(4):551-64
17379065
Pancreatology. 2009;9(3):293-301
19407485