Ellagitannin (BJA3121), an anti‐proliferative natural polyphenol compound, can regulate the expression of MiRNAs in HepG2 cancer cells

MicroRNAs (miRNAs) play an important role in cancers. A number of miRNA expression‐profiling studies have been done to identify the miRNA signatures of cancers from different cellular origin. There is, however, relatively little information on how anticancer agents regulate miRNA expression. Ellagitannin (BJA3121), 1,3‐Di‐O‐galloyl‐4,6‐(s)‐HHDP‐b‐D‐glucopyranose, is a new natural polyphenol compound isolated from Balanophora Japonica MAKINO. Our preliminary results have shown that BJA3121 had antiproliferative effect and modified the expression of different genes in human HepG2 cancer cells. In this study, we further evaluate whether this antineoplastic compound is able to alter miRNA expression in HepG2 cells. We demonstrated for the first time that BJA3121 can regulate the expression of 25 miRNAs, including 17 upregulated and 8 downregulated miRNAs in HepG2 cells. Our results suggested that BJA3121‐modifed miRNA expression can mediate, at least in part, the antiproliferative and multigene regulatory action induced by the compound on HepG2 cancer cells. Copyright © 2009 John Wiley & Sons, Ltd.

[1]  Yuriy Gusev,et al.  Computational analysis of biological functions and pathways collectively targeted by co-expressed microRNAs in cancer , 2007, BMC Bioinformatics.

[2]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[3]  S. Cohen,et al.  The Hippo Pathway Regulates the bantam microRNA to Control Cell Proliferation and Apoptosis in Drosophila , 2006, Cell.

[4]  Gregory J. Hannon,et al.  microRNAs join the p53 network — another piece in the tumour-suppression puzzle , 2007, Nature Reviews Cancer.

[5]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[6]  Shenglin Ma,et al.  A combined treatment TNF-alpha/doxorubicin alleviates the resistance of MCF-7/Adr cells to cytotoxic treatment. , 2006, Biochimica et biophysica acta.

[7]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[8]  John N Weinstein,et al.  MicroRNA expression profiles for the NCI-60 cancer cell panel , 2007, Molecular Cancer Therapeutics.

[9]  Yoshikazu Nakamura,et al.  Altered expression profiles of microRNAs during TPA-induced differentiation of HL-60 cells. , 2004, Biochemical and biophysical research communications.

[10]  Tushar Patel,et al.  Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. , 2006, Gastroenterology.

[11]  Lorena Rossi,et al.  Modification of miR gene expression pattern in human colon cancer cells following exposure to 5-fluorouracil in vitro. , 2007, Pharmacological research.

[12]  Brian S. Roberts,et al.  The colorectal microRNAome. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

[14]  D. Baltimore,et al.  MicroRNAs and immunity: tiny players in a big field. , 2007, Immunity.

[15]  G. Nuovo,et al.  Experimental validation of miRNA targets. , 2008, Methods.

[16]  T. Tanaka,et al.  Caffeoyl, coumaroyl, galloyl, and hexahydroxydiphenoyl glucoses from Balanophora japonica. , 2001, Chemical & pharmaceutical bulletin.

[17]  V. Ambros.  The functions of animal microRNAs , 2004, Nature.

[18]  O. Kovalchuk,et al.  Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure. , 2007, Mutation research.

[19]  C. Croce,et al.  miRNAs, Cancer, and Stem Cell Division , 2005, Cell.

[20]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[21]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Asli Silahtaroglu,et al.  Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. , 2007, Cancer research.

[23]  K. Morimura,et al.  Peroxisome Proliferator-Activated Receptor α Regulates a MicroRNA-Mediated Signaling Cascade Responsible for Hepatocellular Proliferation , 2007, Molecular and Cellular Biology.

[24]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Fatica,et al.  The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation , 2007, Proceedings of the National Academy of Sciences.

[26]  A. Hatzigeorgiou,et al.  TarBase: A comprehensive database of experimentally supported animal microRNA targets. , 2005, RNA.

[27]  Tara L. Naylor,et al.  microRNAs exhibit high frequency genomic alterations in human cancer. , 2006, Proceedings of the National Academy of Sciences of the United States of America.