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

// Kurataka Otsuka 1, 2 , Yusuke Yamamoto 1 and Takahiro Ochiya 1 1 Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan 2 RD 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.