Skip to main content
Log in

Resveratrol alters microRNA expression profiles in A549 human non-small cell lung cancer cells

  • Published:
Molecules and Cells

Abstract

Resveratrol is a plant phenolic phytoalexin that has been reported to have antitumor properties in several types of cancers. In particular, several studies have suggested that resveratrol exerts antiproliferative effects against A549 human non-small cell lung cancer cells; however, its mechanism of action remains incompletely understood. Deregulation of microRNAs (miRNAs), a class of small, noncoding, regulatory RNA molecules involved in gene expression, is strongly correlated with lung cancer. In this study, we demonstrated that resveratrol treatment altered miRNA expression in A549 cells. Using microarray analysis, we identified 71 miRNAs exhibiting greater than 2-fold expression changes in resveratrol-treated cells relative to their expression levels in untreated cells. Furthermore, we identified target genes related to apoptosis, cell cycle regulation, cell proliferation, and differentiation using a miRNA target-prediction program. In conclusion, our data demonstrate that resveratrol induces considerable changes in the miRNA expression profiles of A549 cells, suggesting a novel approach for studying the anticancer mechanisms of resveratrol.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aggarwal, B.B., Bhardwaj, A., Aggarwal, R.S., Seeram, N.P., Shishodia, S., and Takada, Y. (2004). Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 24, 2783–2840.

    PubMed  CAS  Google Scholar 

  • Ambros, V., and Chen, X. (2007). The regulation of genes and genomes by small RNAs. Development 134, 1635–1641.

    Article  PubMed  CAS  Google Scholar 

  • Ambros, V., and Lee, R.C. (2004). Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning. Methods Mol. Biol. 265, 131–158.

    PubMed  CAS  Google Scholar 

  • Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297.

    Article  PubMed  CAS  Google Scholar 

  • Bhat, K.P., and Pezzuto, J.M. (2002). Cancer chemopreventive activity of resveratrol. Ann. N. Y. Acad. Sci. 957, 210–229.

    Article  PubMed  CAS  Google Scholar 

  • Bhat, K.P.L., Kosmeder, J.W.2nd., and Pezzuto, J.M. (2001). Biological effects of resveratrol. Antioxid. Redox. Signal. 3, 1041–1064.

    Article  PubMed  CAS  Google Scholar 

  • Calin, G.A., Ferracin, M., Cimmino, A., Di Leva, G., Shimizu, M., Wojcik, S.E., Iorio, M.V., Visone, R., Sever, N.I., Fabbri, M., et al. (2005). A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N. Engl. J. Med. 353, 1793–1801.

    Article  PubMed  CAS  Google Scholar 

  • Chen, J.F., Mandel, E.M., Thomson, J.M., Wu, Q., Callis, T.E., Hammond, S.M., Conlon, F.L., and Wang, D.Z. (2006). The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat. Genet. 38, 228–233.

    Article  PubMed  CAS  Google Scholar 

  • Cheng, A.M., Byrom, M.W., Shelton, J., and Ford, L.P. (2005). Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 33, 1290–1297.

    Article  PubMed  CAS  Google Scholar 

  • Cho, W.J., Shin, J.M., Kim, J.S., Lee, M.R., Hong, K.S., Lee, J.H., Koo, K.H., Park, J.W., and Kim, K.S. (2009). miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2. Mol. Cells 28, 521–527.

    Article  PubMed  CAS  Google Scholar 

  • Delmas, D., Jannin, B., and Latruffe, N. (2005). Resveratrol: preventing properties against vascular alterations and ageing. Mol. Nutr. Food. Res. 49, 377–395.

    Article  PubMed  CAS  Google Scholar 

  • Eder, M., and Scherr, M. (2005). MicroRNA and lung cancer. N. Engl. J. Med. 352, 2446–2448.

    Article  PubMed  CAS  Google Scholar 

  • Faber, A.C., and Chilles, T.C. (2006). Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: evidence for a novel mechanism involving inhibition of BCL6 signaling. Int. J. Oncol. 29, 1561–1566.

    PubMed  CAS  Google Scholar 

  • Guo L., and Lu, Z. (2010). The fate of miRNA* strand through Evolutionary anlysis: Implication for degradation as carrier strand or potential regulatory molecules? PLoS One 5, e11387

    Article  PubMed  Google Scholar 

  • He, L., Thomson, J.M., Hemann, M.T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S.W., Hannon, G.J., et al. (2005). A microRNA polycistron as a potential human oncogene. Nature 435, 828–833.

    Article  PubMed  CAS  Google Scholar 

  • John, B., Enright, A.J., Aravin, A., Tuschl, T., Sander, C., and Marks, D.S. (2004). Human MicroRNA targets. PLoS Biol. 2, e363.

    Article  PubMed  Google Scholar 

  • Johnson, S.M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K.L., Brown, D., and Slack, F.J. (2005). RAS is regulated by the let-7 microRNA family. Cell 120, 635–647.

    Article  PubMed  CAS  Google Scholar 

  • Kasdallah-Grissa, A., Mornagui, B., Aouani, E., Hammami, M., El May, M., Gharbi, N., Kamoun, A., and El-Fazaa, S. (2007). Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver. Life Sci. 80, 1033–1039.

    Article  PubMed  CAS  Google Scholar 

  • Kim, Y.A., Lee, W.H., Choi, T.H., Rhee, S.H., Park, K.Y., and Choi, Y.H. (2003). Involvement of p21WAF1/CIP1, pRB, Bax and NFkappaB in induction of growth arrest and apoptosis by resveratrol in human lung carcinoma A549 cells. Int. J. Oncol. 23, 1143–1149.

    PubMed  CAS  Google Scholar 

  • Kundu, J.K., and Surh, Y.J. (2004). Molecular basis of chemoprevention by resveratrol: NF-kappaB and AP-1 as potential targets. Mutat. Res. 555, 65–80.

    Article  PubMed  CAS  Google Scholar 

  • Logarajah, S., Hunter, P., Kraman, M., Steele, D., Lakhani, S., Bobrow, L., Venkitaraman, A., and Wagner, S. (2003). BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation. Oncogene 22, 5572–5578.

    Article  PubMed  CAS  Google Scholar 

  • Ma, X.D., Yan, F., Ma, A.D., and Wang, H.J. (2006). Resveratrol induces HepG2 cell apoptosis by depolarizing mitochondrial membrane. Nan Fang Yi Ke Da Xue Xue Bao 26, 406–408.

    PubMed  CAS  Google Scholar 

  • Matsuoka, A., Furuta, A., Ozaki, M., Fukuhara, K., and Miyata, N. (2001). Resveratrol, a naturally occurring polyphenol, induces sister chromatid exchanges in a Chinese hamster lung (CHL) cell line. Mutat. Res. 494, 107–113.

    PubMed  CAS  Google Scholar 

  • Moammir, H.A., Minakshi, N., Vivian, X.F., David, F.J., and Nihal, A. (2006). Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3′-kinase/Akt pathway and Bcl-2 family proteins. Mol. Cancer Ther. 5, 1335–1341.

    Article  Google Scholar 

  • Mollerup, S., Ovrebo, S., and Haugen, A. (2001). Lung carcinogenesis: resveratrol modulates the expression of genes involved in the metabolism of PAH in human bronchial epithelial cells. Int. J. Cancer 92, 18–25.

    Article  PubMed  CAS  Google Scholar 

  • Nana-Sinkam, S.P., and Geraci, M.W. (2006). MicroRNA in lung cancer. J. Thorac. Oncol. 1, 929–931.

    Article  PubMed  Google Scholar 

  • O’Toole, A.S., Miller, S., Haines, N., Zink, M.C., and Serra, M.J. (2006). Comprehensive thermodynamic analysis of 3′doublenucleotide overhangs neighboring Watson-Crick terminal pairs. Nucleic Acids Res. 34, 3338–3344.

    Article  PubMed  Google Scholar 

  • Park, J.S., Kim, K.M., Kim, M.H., Chang, H.J., Baek, M.K., Kim, S.M., and Jung, Y.D. (2009). Resveratrol inhibits tumor cell adhension to endothetial cells by blocking ICAM-1 expression. Anticancer Res. 29, 355–362.

    PubMed  CAS  Google Scholar 

  • Pillai, R.S., Bhattacharyya, S.N., and Filipowicz, W. (2007). Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol. 17, 118–126.

    Article  PubMed  CAS  Google Scholar 

  • Plasterk, R.H. (2006). Micro RNAs in animal development. Cell 124, 877–881.

    Article  PubMed  CAS  Google Scholar 

  • Rana, T.M. (2007). Illuminating the silence: understanding the structure and function of small RNAs. Nat. Rev. Mol. Cell. Biol. 8, 23–36.

    Article  PubMed  CAS  Google Scholar 

  • Revel, A., Raanani, H., Younglai, E., Xu, J., Rogers, I., Han, R., Savouret, J.F., and Casper, R.F. (2003). Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects lung from DNA damage and apoptosis caused by benzo[a]pyrene. J. Appl. Toxicol. 23, 255–261.

    Article  PubMed  CAS  Google Scholar 

  • Schneider, Y., Vincent, F., Duranton, B., Badolo, L., Gosse, F., Bergmann, C., Seiler, N., and Raul, F. (2000). Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett. 158, 85–91.

    Article  PubMed  CAS  Google Scholar 

  • Soleas, G.J., Diamandis, E.P., and Goldberg, D.M. (1997). Resveratrol: a molecule whose time has come? And gone? Clin. Biochem. 30, 91–113.

    Article  PubMed  CAS  Google Scholar 

  • Staudt, L.M., Dent, A.L., Shaffer, A.L., and Yu, X. (1999). Regulation of lymphocyte cell fate decisions and lymphomagenesis by BCL-6. Int. Rev. Immunol. 18, 381–403.

    Article  PubMed  CAS  Google Scholar 

  • Stef, G., Csiszar, A., Lerea, K., Ungvari, Z., and Veress, G. (2006). Resveratrol inhibits aggregation of platelets from high-risk cardiac patients with aspirin resistance. J. Cardiovasc. Pharmacol. 48, 1–5.

    Article  PubMed  CAS  Google Scholar 

  • Stervbo, U., Vang, O., and Bonnesen, C. (2006). Time-and concentration-dependent effects of resveratrol in HL-60 and HepG2 cells. Cell Prolif. 39, 479–493.

    Article  PubMed  CAS  Google Scholar 

  • Stewart, J.R., Artime, M.C., and O’Brian, C.A. (2003). Resveratrol: a candidate nutritional substance for prostate cancer prevention. J. Nutr. 133, 2440S–2443S.

    PubMed  CAS  Google Scholar 

  • Sun, C., Hu, Y., Liu, X., Wu, T., Wang, Y., He, W., and Wei, W. (2006). Resveratrol downregulates the constitutional activation of nuclear factor-kappaB in multiple myeloma cells, leading to suppression of proliferation and invasion, arrest of cell cycle, and induction of apoptosis. Cancer Genet. Cytogenet. 165, 9–19.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, B., Wang, Q., and Pan, X. (2007). MicroRNAs and their regulatory roles in animals and plants. J. Cell. Physiol. 210, 279–289.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sungkwan An.

About this article

Cite this article

Bae, S., Lee, EM., Cha, H.J. et al. Resveratrol alters microRNA expression profiles in A549 human non-small cell lung cancer cells. Mol Cells 32, 243–249 (2011). https://doi.org/10.1007/s10059-011-1037-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10059-011-1037-z

Keywords

Navigation