MicroRNAs (miRNAs) are small non-coding 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 this study, using miRNA microarray, we observed that down-regulation of the Notch-1 pathway, by delta-tocotrienol, correlated with up-regulation of miR-34a, in non-small 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 non-toxic activator of mir-34a which can inhibit NSCLC cell proliferation, induce apoptosis, and inhibit invasion, thus offering a potential starting point for the design of novel anticancer agents. © 2012 Wiley-Liss, Inc.

Copyright © 2012 Wiley-Liss, Inc.

PMID: 22438124 [PubMed - as supplied by publisher] Source: National Library of Medicine.