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Cited by 237MicroRNA in disease regulationSirtuins and Resveratrol in MedicineCancer-related molecular mechanisms research

Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβ signaling pathway in SW480 cells

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Tili, Esmerina, Michaille, Jean-Jacques, Alder, Hansjuerg, Volinia, Stefano, Delmas, Dominique, Latruffe, Norbert, Croce, Carlo M.·2010·Biochemical Pharmacology
DOI 10.1016/j.bcp.2010.07.003PMC PMC3918904
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Abstract

Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural antioxidant with cardiovascular and cancer preventive properties that is currently at the stage of pre-clinical studies for human cancer prevention. Beside its known effects on protein coding genes, one possible mechanism for resveratrol protective activities is by modulating the levels of non-coding RNAs. Here, we analyzed the effects of resveratrol on microRNA populations in human SW480 colon cancer cells. We establish that resveratrol treatment decreases the levels of several oncogenic microRNAs targeting genes encoding Dicer1, a cytoplasmic RNase III producing mature microRNAs from their immediate precursors, tumor-suppressor factors such as PDCD4 or PTEN, as well as key effectors of the TGFβ signaling pathway, while increasing the levels of miR-663, a tumor-suppressor microRNA targeting TGFβ1 transcripts. We also show that, while upregulating several components of the TGFβ signaling pathway such as TGFβ receptors type I (TGFβR1) and type II (TGFβR2), resveratrol decreases the transcriptional activity of SMADs, the main effectors of the canonical TGFβ pathway. Our results establish that protective properties of resveratrol may arise at least in part from its capability to modify the composition of microRNA populations in cells, and suggest that the manipulation of the levels of key microRNAs, such as miR-663, may help to potentiate the anti-cancer and anti-metastatic effects of resveratrol.

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  • Curcumin and resveratrol up-regulate PDCD4-protein levels by inhibiting miR21 expression.

    “Both compounds up-regulate PDCD4-protein levels by inhibiting mir21 expression [93,94,95,96].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [95]

    Results §3.1 reports that resveratrol reduced miR-21 in SW480 cells, and Results §3.2 reports that PDCD4 levels increased after resveratrol treatment. The Discussion identifies PDCD4 as a miR-21 target, but these passages do not establish that miR-21 inhibition caused the PDCD4 increase. They do not address curcumin. (LLM, conf=0.88)

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References 53 · Cited by 237

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  1. [1]Tenesa A Dunlop MG New insights into the aetiology of colorectal cancer from genome-wide association studies Nat Rev Genet 2009 10 3538 19434079
  2. [2]Jemal A Siegel R Ward E Murray T Xu J Smigal C Cancer statistics, 2006 Cancer J Clin 2006 56 106 30 16514137
  3. [3]Olsson L Lindblom A Family hitory of colorectal cancer in a Sweden county Fam Cancer 2003 2 87 93 14574157
  4. [5]Cheah PY Recent advances in colorectal cancer genetics and diagnostics Crit Rev Oncol Hematol 2009 69 45 55 18774731
  5. [6]Kinzler KW Vogelstein B Lessons from hereditary colorectal cancer Cell 1996 87 159 70 8861899
  6. [7]Giles RH van Es JH Clevers H Caught up in a Wnt storm: Wnt signaling in cancer Biochim Biophys Acta 2003 1653 1 24 12781368
  7. [8]Massagué J Blain SW Lo RS TGFbeta signaling in growth control, cancer, and heritable disorders Cell 2000 103 295 309 11057902
  8. [9]Akhurst RJ TGF beta signaling in health and disease Nat Genet 2004 36 790 2 15284845
  9. [10]Elliott RL Blobe GC Role of transforming growth factor beta in human cancer J Clin Oncol 2005 23 2078 93 15774796
  10. [11]Massagué J TGFbeta in cancer Cell 2008 134 215 30 18662538 PMC3512574
  11. [12]Padua D Massagué J Role of TGFbeta in metastasis Cell Res 2009 1 89 102 19050696
  12. [13]Tian M Schiemann WP The TGF-beta paradox in human cancer: an update Future Oncol 2009 5 259 71 19284383 PMC2710615
  13. [14]Langenskiöld M Holmdahl L Falk P Angenete E Ivarsson ML Increased TGF-beta 1 protein expression in patients with advanced colorectal cancer J Surg Oncol 2008 97 409 15 18176914
  14. [15]Calin GA Croce CM MiRNA signatures in human cancers Nat Rev Cancer 2006 6 857 66 17060945
  15. [16]Tili E Michaille JJ Gandhi V Plunkett W Sampath D Calin GA 2007. miRNAs and their potential for use against cancer and other diseases Future Oncol 2007 5 521 7 17927518
  16. [17]Krichevsky AM Gabriely G miR-21: a small multi-faceted RNA J Cell Mol Med 2009 13 39 53 19175699 PMC3823035
  17. [18]Aqeilan RI Calin GA Croce CM miR-15a and miR-16-1 in cancer: discovery, function and future perspectives Cell Death Differ 2010 17 215 20 19498445
  18. [19]Rossi S Kopetz S Davuluri R Hamilton SR Calin GA MicroRNAs, ultraconserved genes and colorectal cancers Int J Biochem Cell Biol 2009 10.1016/j.biocel.2009.05.018 19497386 · DOI
  19. [20]Yang L Belaguli N Berger DH MicroRNA and Colorectal cancer World J Surg 2009 33 638 4 19123024
  20. [21]Nicoloso MS Spizzo R Shimizu M Rossi S Calin GA MicroRNAs – the micro steering wheel of tumor metastases Nat Rev Cancer 2009 9 293 302 19262572
  21. [22]Csiszar A Smith K Labinskyy N Orosz Z Rivera A Ungvari Z Resveratrol attenuates TNFa-induced activation of coronary arterial endothelial cells: role of NF-kB inhibition Am J Physiol Heart Circ Physiol 2006 291 H1694 9 16973825
  22. [23]Shankar S Singh G Srivastava RK Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential Front Biosci 2007 12 4839 54 17569614
  23. [24]Bishayee A Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials Cancer Prev Res 2009 2 409 18 19401532
  24. [25]Athar M Back JH Tang X Kim KH Kopelovich L Bickers DR Resveratrol: a review of preclinical studies for human cancer prevention Toxicol Appl Pharmacol 2007 224 274 83 17306316 PMC2083123
  25. [26]Delmas D Rébé C Micheau O Athias A Gambert P Grazide S Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells Oncogene 2004 23 8979 86 15480430
  26. [27]Lin SL Chiang A Chang D Ying SY Loss of miR-146a function in hormone-refractory prostate cancer RNA 2008 14 417 24 18174313 PMC2248249
  27. [28]Volinia S Calin GA Liu CG Ambs S Cimmino A Petrocca F A microRNA expression signature of human solid tumors defines cancer gene targets Proc Natl Acad Sci U S 2006 103 2257 61 PMC1413718 16461460
  28. [29]Slaby O Svoboda M Fabian P Smerdova T Knoflickova D Bednarikova M Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer Oncology 2007 72 397 402 18196926
  29. [30]Selcuklu SD Donoghue MT Spillane C miR-21 as a key regulator of oncogenic processes Biochem Soc Trans 2009 37 918 25 19614619
  30. [31]Chen Y Knösel T Kristiansen G Pietas A Garber ME Matsuhashi S Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis J Pathol 200 200 640 6 12898601
  31. [32]Mudduluru G Medved F Grobholz R Jost C Gruber A Leupold JH Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer Cancer 2007 110 1697 707 17849461
  32. [33]Martello G Rosato A Ferrari F Manfrin A Cordenonsi M Dupont S A microRNA targeting Dicer for metastasis control Cell 2010 141 1195 207 20603000
  33. [34]Lu J Getz G Miska EA Alvarez-Saavedra E Lamb J Peck D MicroRNA expression profiles classify human cancers Nature 2005 435 834 8 15944708
  34. [35]Kumar MS Lu J Mercer KL Golub TR Jacks T Impaired microRNA processing enhances cellular transformation and tumorigenesis Nat Genet 2007 39 673 7 17401365
  35. [36]Ozen M Creighton CJ Ozdemir M Ittmann M Widespread deregulation of microRNA expression in human prostate cancer Oncogene 2008 27 1788 9 17891175
  36. [37]Leibovitz A Stinson JC McCombs WB 3rd McCoy CE Mazur KC Mabry ND Classification of human colorectal adenocarcinoma cell lines Cancer Res 1976 36 4562 69 1000501
  37. [38]Hussain SP Harris CC Inflammation and cancer: an ancient link with novel potentials Int J Cancer 2007 121 2373 80 17893866
  38. [39]Mantovani A Allavena P Sica A Balkwill F Cancer-related inflammation Nature 2008 454 436 44 18650914
  39. [40]Schetter AJ Heegaard NH Harris CC Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways Carcinogenesis 2010 31 37 49 19955394 PMC2802675
  40. [41]Wahl SM Wen J Moutsopoulos N TGF-beta: a mobile purveyor of immune privilege Immunol Rev 2006 10 213 213 27 16972906
  41. [42]Davis BN Hilyard AC Lagna G Hata A SMAD proteins control DROSHA-mediated microRNA maturation Nature 2008 454 56 61 18548003 PMC2653422
  42. [43]Buratti E De Conti L Stuani C Romano M Baralle M Baralle F Nuclear factor TDP-43 can affect selected microRNA levels FEBS J 2010 277 2268 81 20423455
  43. [44]Pan J Hu H Zhou Z Sun L Peng L Yu L Tumor-suppressive miR-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells Oncol Rep 2010 24 105 12 20514450
  44. [45]Yoo YA Kang MH Kim JS Oh SC Sonic hedgehog signaling promotes motility and invasiveness of gastric cancer cells through TGF-beta-mediated activation of the ALK5-Smad3 pathway Carcinogenesis 2008 29 480 90 18174246
  45. [46]Xiao C Colado DP Galler G Thai TH Patterson HC Wang J MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb Cell 2007 131 146 59 17923094
  46. [47]Kuchen S Resch W Yamane A Kuo N Li Z Chakraborty T Regulation of microRNA expression and abundance during lymphopoiesis Immunity 2010 32 828 39 20605486 PMC2909788
  47. [48]Matsuzaki K Kitano C Murata M Sekimoto G Yoshida K Uemura Y Smad2 and Smad3 phosphorylated at both linker and COOH-terminal regions transmit malignant TGF-beta signal in later stages of human colorectal cancer Cancer Res 2009 69 5321 30 19531654
  48. [49]Yan X Liu Z Chen Y Regulation of TGF-β by Smad7 Acta Biochim Biophys Sin 2009 41 263 72 19352540 PMC7110000

Authors
Tili, E., Michaille, J.-J., Alder, H., Volinia, S., Delmas, D., Latruffe, N., & Croce, C. M.
Affiliations
  • The Ohio State University (US)
  • Inserm (FR)
Corresponding author
Michaille, Jean-Jacques
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2010-12
Volume
80
Issue
12
Pages
2057-2065
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/j.bcp.2010.07.003
PMC
PMC3918904
OpenAlex
W2077838973
Cited by
237
References
53
Citations by year
2026: 6 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 20 · 2021: 13 · 2020: 12 · 2019: 19 · 2018: 22 · 2017: 18 · 2016: 24 · 2015: 14 · 2014: 15 · 2013: 21 · 2012: 18
FWCI
5.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
Funders
  • Ohio State University
  • Comprehensive Cancer Center, City of Hope
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
resveratrol, microRNA, colon cancer, SW480 cells, TGFβ signaling pathway, Smad transcription factors, DICER1, PDCD4, PTEN, miR-663, TGF-beta receptor, tumor suppressor microRNA, non-coding RNA, antimetastatic activity
MeSH terms
Resveratrol, Antineoplastic Agents, Antioxidants, Humans, Stilbenes, Signal Transduction, Oncogene Proteins, Transforming Growth Factor beta, Tumor Suppressor Proteins, MicroRNAs, Cell Line, Tumor, Smad Proteins, Transforming Growth Factor beta1

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