Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA.
Int J Cancer. 2012 Dec 1;131(11):2668-77. doi: 10.1002/ijc.27549. Epub 2012 Jun 26.
MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in regulating various cellular functions by transcriptional silencing. miRNAs can function as either oncogenes or tumor suppressors (oncomirs), depending on cancer types. In our study, using miRNA microarray, we observed that downregulation of the Notch-1 pathway, by delta-tocotrienol, correlated with upregulation of miR-34a, in nonsmall cell lung cancer cells (NSCLC). Moreover, re-expression of miR-34a by transfection in NSCLC cells resulted in inhibition of cell growth and invasiveness, induction of apoptosis and enhanced p53 activity. Furthermore, cellular mechanism studies revealed that induction of miR-34a decreased the expression of Notch-1 and its downstream targets including Hes-1, Cyclin D1, Survivin and Bcl-2. Our findings suggest that delta-tocotrienol is a nontoxic activator of mir-34a which can inhibit NSCLC cell proliferation, induce apoptosis and inhibit invasion, and thus offering a potential starting point for the design of novel anticancer agents.
微小 RNA（miRNA）是一类小的非编码 RNA，通过转录沉默在调节各种细胞功能方面发挥着关键作用。miRNA 可以作为癌基因或肿瘤抑制因子（oncomirs）发挥作用，具体取决于癌症类型。在我们的研究中，使用 miRNA 微阵列，我们观察到 delta-生育三烯酚通过下调 Notch-1 通路，与 miR-34a 的上调相关，在非小细胞肺癌细胞（NSCLC）中。此外，通过转染在 NSCLC 细胞中重新表达 miR-34a 导致细胞生长和侵袭性的抑制、凋亡的诱导和 p53 活性的增强。此外，细胞机制研究表明，诱导 miR-34a 降低了 Notch-1 及其下游靶标包括 Hes-1、Cyclin D1、Survivin 和 Bcl-2 的表达。我们的研究结果表明，delta-生育三烯酚是一种非毒性的 mir-34a 激活剂，可抑制 NSCLC 细胞增殖、诱导凋亡和抑制侵袭，从而为设计新型抗癌药物提供了一个潜在的起点。
