Otsuka Kurataka, Yamamoto Yusuke, Ochiya Takahiro
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
R&D Division, Kewpie Corporation Sengawa Kewport, Chofu-shi, Tokyo 182-0002, Japan.
Oncotarget. 2018 May 15;9(37):24718-24730. doi: 10.18632/oncotarget.25339.
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 (, , and ) via the p53 pathway and then by suppressing heterogeneous nuclear ribonucleoprotein A1 (), which is associated with tumorigenesis and tumor progression. Notably, was directly regulated by and , the expression of which were mediated by resveratrol. Moreover, we found that resveratrol exerts broad effects on the -related pre-mRNA splicing pathway. Our data provide novel insights into the regulatory roles of resveratrol for preventing and treating of diseases.
某些生活方式,如不健康的饮食习惯,与包括癌症在内的多种疾病风险增加有关。最近,一些天然存在的化合物,如白藜芦醇,已被证明能以积极的方式调节微小RNA(miRNA)的表达;这种调节活性可能对癌症预防和治疗有益。白藜芦醇是一种多功能的多酚类植物抗毒素,已知具有抗肿瘤和抗炎作用,并能调节miRNA表达。然而,我们对其潜在分子机制的理解仍不完整,即白藜芦醇如何通过调节miRNA和致癌靶基因表达来控制癌细胞生长以抑制疾病进展。在这里,我们表明白藜芦醇通过p53途径诱导肿瘤抑制性miRNA(、和),然后抑制与肿瘤发生和肿瘤进展相关的不均一核核糖核蛋白A1(),从而控制乳腺癌细胞增殖。值得注意的是,直接受和调控,而它们的表达由白藜芦醇介导。此外,我们发现白藜芦醇对相关前体mRNA剪接途径有广泛影响。我们的数据为白藜芦醇在疾病预防和治疗中的调节作用提供了新的见解。