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Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92
- Source :
- Oncogene. 26(41)
- Publication Year :
- 2007
-
Abstract
- Amplification and overexpression of the miR-17-92 microRNAs (miRNA) cluster at 13q31.3 has recently reported, with pointers to functional involvement in the development of B-cell lymphomas and lung cancers. In the present study, we show that inhibition of miR-17-5p and miR-20a with antisense oligonucleotides (ONs) can induce apoptosis selectively in lung cancer cells overexpressing miR-17-92, suggesting the possibility of 'OncomiR addiction' to expression of these miRNAs in a subset of lung cancers. In marked contrast, antisense ONs against miR-18a and miR-19a did not exhibit such inhibitory effects, whereas inhibition of miR-92-1 resulted in only modest reduction of cell growth, showing significant distinctions among miRNAs of the miR-17-92 cluster in terms of their roles in cancer cell growth. During the course of this study, we also found that enforced expression of a genomic region, termed C2, residing 3' to miR-17-92 in the intron 3 of C13orf25 led to marked growth inhibition in association with double stranded RNA-dependent protein kinase activation. Finally, this study also revealed that the vast majority of C13orf25 transcripts are detected as Drosha-processed cleavage products on Northern blot analysis and that a novel polyadenylation site is present 3' to the miR-17-92 cluster and 5' to the C2 region. Taken together, the present findings contribute towards better understanding of the oncogenic roles of miR-17-92, which might ultimately lead to the future translation into clinical applications.
- Subjects :
- Cancer Research
Lung Neoplasms
Transcription, Genetic
Apoptosis
Biology
medicine.disease_cause
chemistry.chemical_compound
Open Reading Frames
RNA interference
Cell Line, Tumor
microRNA
Genetics
medicine
In Situ Nick-End Labeling
Gene silencing
Humans
Molecular Biology
Chromosomes, Human, Pair 13
Cell growth
Oncomir
Oligonucleotides, Antisense
MicroRNAs
chemistry
Cancer cell
Cancer research
Growth inhibition
Carcinogenesis
Cell Division
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 26
- Issue :
- 41
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....64fcb77dbe7aaa10ae79a6cb2647474b