title: Delta-tocotrienol suppresses Notch-1 pathway by upregulating miR-34a in nonsmall cell lung cancer cells.
abstract: 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.
authors.affiliation: Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Ji
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Andreea
authors.initials: A
authors.lastname: Geamanu
authors.forename: Arvind
authors.initials: A
authors.lastname: Goja
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Smiti V
authors.initials: SV
authors.lastname: Gupta
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000077022:Survivin; D000072056:Transcription Factor HES-1; D014162:Transfection / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019938:Cyclin D1; D018398:Homeodomain Proteins; D051034:Inhibitor of Apoptosis Proteins; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D000077022:Survivin; D000072056:Transcription Factor HES-1; D016159:Tumor Suppressor Protein p53; D014810:Vitamin E; C107489:BIRC5 protein, human; C522425:MIRN34 microRNA, human; C497761:NOTCH1 protein, human; C495901:TP53 protein, human; C078493:HES1 protein, human; C082097:tocotrienol, delta