RNA-binding protein NONO promotes breast cancer proliferation by post-transcriptional regulation of SKP2 and E2F8

Kaori Iino, Yuichi Mitobe, Kazuhiro Ikeda, Ken ichi Takayama, Takashi Suzuki, Hidetaka Kawabata, Yutaka Suzuki, Kuniko Horie-Inoue, Satoshi Inoue

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The majority of breast cancers are primarily hormone-sensitive and can be managed by endocrine therapy, although therapy-resistant or hormone-refractory cancers need alternative treatments. Recently, increasing attention is being paid to RNA-binding proteins (RBP) in cancer pathophysiology. The precise role of RBP in breast cancer, however, remains to be clarified. We herein show that an RBP non-POU domain-containing octamer binding (NONO) plays a critical role in the pathophysiology of breast cancers regardless of their hormone dependency. Clinicopathological and immunohistochemical study of 127 breast cancer cases showed that NONO is a significant independent prognostic factor for breast cancer patients. Notably, siRNA-mediated NONO knockdown substantially repressed the proliferation of both hormone-sensitive MCF-7 and hormone-refractory MB-MDA-231 breast cancer cells. Integrative analysis combined with expression microarray and RIP-sequencing (RNA immunoprecipitation-sequencing) showed that NONO post-transcriptionally regulates the expression of cell proliferation-related genes by binding to their mRNAs, as exemplified by S-phase-associated kinase 2 and E2F transcription factor 8. Overall, these results suggest that NONO is a key regulator for breast cancer proliferation through the pre-mRNA splicing of cell proliferation-related genes and could be a potential new diagnostic and therapeutic target for advanced disease.

Original languageEnglish
Pages (from-to)148-159
Number of pages12
JournalCancer science
Volume111
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1

Keywords

  • NONO
  • RNA-binding protein
  • breast cancer
  • post-transcriptional regulation
  • splicing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Iino, K., Mitobe, Y., Ikeda, K., Takayama, K. I., Suzuki, T., Kawabata, H., Suzuki, Y., Horie-Inoue, K., & Inoue, S. (2020). RNA-binding protein NONO promotes breast cancer proliferation by post-transcriptional regulation of SKP2 and E2F8. Cancer science, 111(1), 148-159. https://doi.org/10.1111/cas.14240