Studies on microRNA

The tumor macroenvironment and microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy.

Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers or therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21, may influence response to chemotherapy in many tumor types, including PDAC. In our studies we evaluate pivotal miRNAs in PDAC and thoracic cancers, focusing on their role in chemoresistance through multiple molecular mechanisms.

Our main articles related to this project

1. Frampton AE, Castellano L, Colombo T, Giovannetti E, Krell J, Jacob J, Pellegrino L, Roca-Alonso L, Funel N, Gall TM, Ahmad R, Habib NA, Knösel T, Stebbing J, Jiao LR.
   Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression.
   Lancet. 2015;385 Suppl 1:S37.
   Link: www.ncbi.nlm.nih.gov/pubmed/26312859
2. Frampton AE, Krell J, Jamieson NB, Gall TM, Giovannetti E, Funel N, Mato Prado M, Krell D, Habib NA, Castellano L, Jiao LR, Stebbing J.
   microRNAs with prognostic significance in pancreatic ductal adenocarcinoma: A meta-analysis.
   Eur J Cancer. 2015 Jul;51(11):1389-404.
   Link: www.ncbi.nlm.nih.gov/pubmed/26002251
3. Le Large TY, Frampton AE, Meijer LL, Stebbing J, Kazemier G, Giovannetti E.
   Usefulness of Measuring microRNAs in Bile and Plasma for Pancreatic Ductal Adenocarcinoma Diagnosis.
   Am J Gastroenterol. 2015 May;110(5):768-9.
   Link: www.ncbi.nlm.nih.gov/pubmed/25942302
4. Gandellini P, Giovannetti E, Nicassio F.
   MicroRNAs in Cancer Management: Big Challenges for Small Molecules.
   Biomed Res Int. 2015;2015:982156.
   Link: www.ncbi.nlm.nih.gov/pubmed/25879042
   Free pdf: click here
5. Garajová I, Le Large TY, Frampton AE, Rolfo C, Voortman J, Giovannetti E.
   Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer
   Biomed Res Int. 2014;2014:678401
   Link: www.ncbi.nlm.nih.gov/pubmed/25250326
   Free pdf: click here
6. Maftouh M, Avan A, Funel N, Frampton AE, Fiuji H, Pelliccioni S, Castellano L, Galla V, Peters GJ, Giovannetti E.
   miR-211 modulates gemcitabine activity through downregulation of ribonucleotide reductase and inhibits the invasive behavior of pancreatic cancer cells
   Nucleosides Nucleotides Nucleic Acids. 2014;33(4-6):384-93
   Link: www.ncbi.nlm.nih.gov/pubmed/24940696
7. Frampton AE, Giovannetti E, Jamieson NB, Krell J, Gall TM, Stebbing J, Jiao LR, Castellano L.
   A microRNA meta-signature for pancreatic ductal adenocarcinoma
   Expert Rev Mol Diagn. 2014 Apr;14(3):267-71
   Link: www.ncbi.nlm.nih.gov/pubmed/24575833
8. Rolfo C, Fanale D, Hong DS, Tsimberidou AM, Piha-Paul SA, Pauwels P, Van Meerbeeck JP, Caruso S, Bazan V, Cicero G, Russo A.
   Impact of microRNAs in resistance to chemotherapy and novel targeted agents in non-small cell lung cancer
   Curr Pharm Biotechnol. 2014;15(5):475-85
   Link: www.ncbi.nlm.nih.gov/pubmed/24846062
9. Frampton AE, Castellano L, Colombo T, Giovannetti E, Krell J, Jacob J, Pellegrino L, Roca-Alonso L, Funel N, Gall TM, De Giorgio A, Pinho FG, Fulci V, Britton DJ, Ahmad R, Habib NA, Coombes RC, Harding V, Knösel T, Stebbing J, Jiao LR.
   MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression
   Gastroenterology. 2014 Jan;146(1):268-77.e18
   Link: www.ncbi.nlm.nih.gov/pubmed/24120476
10. Frampton AE, Krell J, Kazemier G, Giovannetti E.
    Serum miR-1290 as a marker of pancreatic cancer–letter
    Clin Cancer Res. 2013 Sep 15;19(18):5250-1
    Link: www.ncbi.nlm.nih.gov/pubmed/23888071
11. Maftouh M, Avan A, Galvani E, Peters GJ, Giovannetti E.
    Molecular mechanisms underlying the role of microRNAs in resistance to epidermal growth factor receptor-targeted agents and novel therapeutic strategies for treatment of non-small-cell lung cancer
    Crit Rev Oncog. 2013;18(4):317-26
    Link: www.ncbi.nlm.nih.gov/pubmed/23614618
12. Frampton AE, Krell J, Giovannetti E, Krell D, Stebbing J, Castellano L, Jiao LR.
    Defining a prognostic molecular profile for ductal adenocarcinoma of the pancreas highlights known key signaling pathways
    Expert Rev Anticancer Ther. 2012 Oct;12(10):1275-8
    Link: www.ncbi.nlm.nih.gov/pubmed/23176615
13. Frampton AE, Krell J, Giovannetti E, Jiao LR, Stebbing J.
    Role of miRNAs in the response to anticancer therapy
    Pharmacogenomics. 2012 Nov;13(15):1663-6
    Link: www.ncbi.nlm.nih.gov/pubmed/23171328
14. Giovannetti E, van der Velde A, Funel N, Vasile E, Perrone V, Leon LG, De Lio N, Avan A, Caponi S, Pollina LE, Gallá V, Sudo H, Falcone A, Campani D, Boggi U, Peters GJ.
    High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer
    PLoS One. 2012;7(11):e49145
    Link: www.ncbi.nlm.nih.gov/pubmed/23155457
    Free pdf: click here
15. Caponi S, Funel N, Frampton AE, Mosca F, Santarpia L, Van der Velde AG, Jiao LR, De Lio N, Falcone A, Kazemier G, Meijer GA, Verheul HM, Vasile E, Peters GJ, Boggi U, Giovannetti E.
    The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms
    Ann Oncol. 2013 Mar;24(3):734-41
    Link: www.ncbi.nlm.nih.gov/pubmed/23139258
16. Hodzic J, Giovannetti E, Diosdado B, Adema AD, Peters GJ.
    Regulation of deoxycytidine kinase expression and sensitivity to gemcitabine by micro-RNA 330 and promoter methylation in cancer cells
    Nucleosides Nucleotides Nucleic Acids. 2011 Dec;30(12):1214-22
    Link: www.ncbi.nlm.nih.gov/pubmed/22132977
17. Giovannetti E, Erozenci A, Smit J, Danesi R, Peters GJ.
    Molecular mechanisms underlying the role of microRNAs (miRNAs) in anticancer drug resistance and implications for clinical practice.
    Crit Rev Oncol Hematol. 2012 Feb;81(2):103-22
    Link: www.ncbi.nlm.nih.gov/pubmed/21546262
18. Hwang JH, Voortman J, Giovannetti E, Steinberg SM, Leon LG, Kim YT, Funel N, Park JK, Kim MA, Kang GH, Kim SW, Del Chiaro M, Peters GJ, Giaccone G.
    Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer
    PLoS One. 2010 May 14;5(5):e10630
    Link: www.ncbi.nlm.nih.gov/pubmed/20498843
    Free pdf: click here
19. Giovannetti E, Funel N, Peters GJ, Del Chiaro M, Erozenci LA, Vasile E, Leon LG, Pollina LE, Groen A, Falcone A, Danesi R, Campani D, Verheul HM, Boggi U.
    MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity
    Cancer Res. 2010 Jun 1;70(11):4528-38
    Link: www.ncbi.nlm.nih.gov/pubmed/20460539
    Free pdf: click here

For our ongoing studies on the role of microRNA in PDAC, in collaboration with Prof. Kazemier (Dept. Surgery, VUmc) we recently obtained a generous grant from the Bennink Foundation, as reported in their website: www.benninkfoundation.com