Oncotarget

Research Papers:

Regulatory role of resveratrol, a microRNA-controlling compound, in HNRNPA1 expression, which is associated with poor prognosis in breast cancer

Kurataka Otsuka, Yusuke Yamamoto and Takahiro Ochiya _

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Oncotarget. 2018; 9:24718-24730. https://doi.org/10.18632/oncotarget.25339

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Abstract

Kurataka Otsuka1,2, Yusuke Yamamoto1 and Takahiro Ochiya1

1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan

2R&D Division, Kewpie Corporation Sengawa Kewport, Chofu-shi, Tokyo 182-0002, Japan

Correspondence to:

Takahiro Ochiya, email: tochiya@ncc.go.jp

Kurataka Otsuka, email: kurotsuk@ncc.go.jp, kurataka_otsuka@kewpie.co.jp

Keywords: resveratrol; microRNA; HNRNPA1; breast cancer; diet

Received: November 21, 2017     Accepted: April 18, 2018     Published: May 15, 2018

ABSTRACT

Certain lifestyles, such as unhealthy eating habits, are associated with an increased risk for several diseases, including cancer. Recently, some naturally occurring compounds, such as resveratrol, have been shown to regulate microRNA (miRNA) expression in a positive manner; this regulatory activity is likely to be advantageous for cancer prevention and treatment. Resveratrol, a multi-functional polyphenolic phytoalexin, has been known to exert anti-tumorigenic and anti-inflammatory effects and to regulate miRNA expression. However, our understanding of the underlying molecular mechanisms whereby resveratrol controls cancer cell growth via the regulation of miRNA and oncogenic target gene expression to inhibit disease progression remains incomplete. Here we show that resveratrol controls breast cancer cell proliferation by inducing tumor-suppressive miRNAs (miR-34a, miR-424, and miR-503) via the p53 pathway and then by suppressing heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), which is associated with tumorigenesis and tumor progression. Notably, HNRNPA1 was directly regulated by miR-424 and miR-503, the expression of which were mediated by resveratrol. Moreover, we found that resveratrol exerts broad effects on the HNRNPA1-related pre-mRNA splicing pathway. Our data provide novel insights into the regulatory roles of resveratrol for preventing and treating of diseases.


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