ASBEL, an ANA/BTG3 antisense transcript required for tumorigenicity of ovarian carcinoma

Mammalian genomes encode numerous antisense non-coding RNAs, which are assumed to be involved in the regulation of the sense gene expression. However, the mechanisms of their action and involvement in the development of diseases have not been well elucidated. The ANA/BTG3 protein is an antiprolifera...

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Bibliographic Details
Published in:Scientific reports 2013-02, Vol.3 (1), p.1305, Article 1305
Main Authors: Yanagida, Satoshi, Taniue, Kenzui, Sugimasa, Hironobu, Nasu, Emiko, Takeda, Yasuko, Kobayashi, Mana, Yamamoto, Tadashi, Okamoto, Aikou, Akiyama, Tetsu
Format: Article
Language:English
Subjects:
631/337/384/2568
631/67/1517/1709
631/80/389/2052
631/80/82/23
Antisense RNA
Apoptosis - genetics
Biological Transport
Carcinoma - genetics
Carcinoma - metabolism
Cell Line, Tumor
Cell Nucleus - metabolism
Cell Transformation, Neoplastic
Cytoplasm - metabolism
Female
Gene expression
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene Order
Genomes
Humanities and Social Sciences
Humans
multidisciplinary
Nuclei
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Prostate
Proteins
Proteins - genetics
Proteins - metabolism
RNA, Antisense
RNA, Untranslated - genetics
RNA, Untranslated - metabolism
Science
Transcription
Transcription, Genetic
Tumorigenesis
Tumorigenicity
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Summary:Mammalian genomes encode numerous antisense non-coding RNAs, which are assumed to be involved in the regulation of the sense gene expression. However, the mechanisms of their action and involvement in the development of diseases have not been well elucidated. The ANA/BTG3 protein is an antiproliferative protein whose expression is downregulated in prostate and lung cancers. Here we show that an antisense transcript of the ANA/BTG3 gene, termed ASBEL , negatively regulates the levels of ANA/BTG3 protein, but not of ANA/BTG3 mRNA and is required for proliferation and tumorigenicity of ovarian clear cell carcinoma. We further show that knockdown of ANA/BTG3 rescues growth inhibition caused by ASBEL knockdown. Moreover, we demonstrate that ASBEL forms duplexes with ANA/BTG3 mRNA in the nucleus and suppresses its cytoplasmic transportation. Our findings illustrate a novel function for an antisense transcript that critically promotes tumorigenesis by suppressing translation of the sense gene by inhibiting its cytoplasmic transportation.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep01305