Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92

H. Matsubara, T. Takeuchi, E. Nishikawa, K. Yanagisawa, Y. Hayashita, H. Ebi, H. Yamada, Motoshi Suzuki, M. Nagino, Y. Nimura, H. Osada, T. Takahashi

Research output: Contribution to journalArticle

276 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6099-6105
Number of pages7
JournalOncogene
Volume26
Issue number41
DOIs
Publication statusPublished - 06-09-2007
Externally publishedYes

Fingerprint

Antisense Oligonucleotides
MicroRNAs
Lung Neoplasms
Apoptosis
Growth
eIF-2 Kinase
Polyadenylation
Double-Stranded RNA
B-Cell Lymphoma
Northern Blotting
Introns
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Matsubara, H., Takeuchi, T., Nishikawa, E., Yanagisawa, K., Hayashita, Y., Ebi, H., ... Takahashi, T. (2007). Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene, 26(41), 6099-6105. https://doi.org/10.1038/sj.onc.1210425
Matsubara, H. ; Takeuchi, T. ; Nishikawa, E. ; Yanagisawa, K. ; Hayashita, Y. ; Ebi, H. ; Yamada, H. ; Suzuki, Motoshi ; Nagino, M. ; Nimura, Y. ; Osada, H. ; Takahashi, T. / Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. In: Oncogene. 2007 ; Vol. 26, No. 41. pp. 6099-6105.
@article{998e5ea94a214f77a1936413770d7417,
title = "Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92",
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.",
author = "H. Matsubara and T. Takeuchi and E. Nishikawa and K. Yanagisawa and Y. Hayashita and H. Ebi and H. Yamada and Motoshi Suzuki and M. Nagino and Y. Nimura and H. Osada and T. Takahashi",
year = "2007",
month = "9",
day = "6",
doi = "10.1038/sj.onc.1210425",
language = "English",
volume = "26",
pages = "6099--6105",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "41",

}

Matsubara, H, Takeuchi, T, Nishikawa, E, Yanagisawa, K, Hayashita, Y, Ebi, H, Yamada, H, Suzuki, M, Nagino, M, Nimura, Y, Osada, H & Takahashi, T 2007, 'Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92', Oncogene, vol. 26, no. 41, pp. 6099-6105. https://doi.org/10.1038/sj.onc.1210425

Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. / Matsubara, H.; Takeuchi, T.; Nishikawa, E.; Yanagisawa, K.; Hayashita, Y.; Ebi, H.; Yamada, H.; Suzuki, Motoshi; Nagino, M.; Nimura, Y.; Osada, H.; Takahashi, T.

In: Oncogene, Vol. 26, No. 41, 06.09.2007, p. 6099-6105.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92

AU - Matsubara, H.

AU - Takeuchi, T.

AU - Nishikawa, E.

AU - Yanagisawa, K.

AU - Hayashita, Y.

AU - Ebi, H.

AU - Yamada, H.

AU - Suzuki, Motoshi

AU - Nagino, M.

AU - Nimura, Y.

AU - Osada, H.

AU - Takahashi, T.

PY - 2007/9/6

Y1 - 2007/9/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34447101200&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447101200&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1210425

DO - 10.1038/sj.onc.1210425

M3 - Article

VL - 26

SP - 6099

EP - 6105

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 41

ER -

Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 2007 Sep 6;26(41):6099-6105. https://doi.org/10.1038/sj.onc.1210425