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

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.

• Authors: Kaori Iino, Yuichi Mitobe, Kazuhiro Ikeda, Ken-Ichi Takayama, Takashi Suzuki, Hidetaka Kawabata, Yutaka Suzuki, Kuniko Horie-Inoue, Satoshi Inoue
• Journal: Cancer science (Cancer Sci) Vol. 111 Issue 1 Pg. 148-159 (Jan 2020) ISSN: 1349-7006 [Electronic] England
• PMID: 31733123 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• DNA-Binding Proteins
• E2F8 protein, human
• NONO protein, human
• RNA, Messenger
• RNA-Binding Proteins
• Repressor Proteins
• S-Phase Kinase-Associated Proteins
• SKP2 protein, human

Topics

• Breast Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Gene Expression Regulation (genetics)
• Humans
• Immunoprecipitation (methods)
• MCF-7 Cells
• RNA Processing, Post-Transcriptional (genetics)
• RNA, Messenger (genetics)
• RNA-Binding Proteins (genetics)
• Repressor Proteins (genetics)
• S-Phase Kinase-Associated Proteins (genetics)