Micrornas Could Be Implicated in Progression of Mycosis Fungoides
Rebeca Manso-Alonso, Socorro Maria Rodriguez-Pinilla, Nerea Martinez Magunacelaya, Margarita Sanchez-Beato, Maria Elena Rodriguez, Itziar Rana Tomas, Veronica Monsalvez, Jose Luis Rodriguez Peralto, Pablo L Ortiz Romero, Miguel Angel Piris. Fundacion Jimenez Diaz, Madrid, Spain; IFIMAV, Santander, Spain; Fundación Investigación Biomédica, Hospital Universitario, Puerta de Hierro-Majadahonda, Madrid, Spain; CNIO, Madrid, Spain; Hospital de Torrejón, Madrid, Spain; Hospital Universitario 12 de Octubre, Madrid, Spain; Hospital Marques de Valdecilla, Santander, Spain
Background: INTRODUCTION: Mycosis fungoides (MF) is an epidermotropic, primary cutaneous T-cell lymphoma (CTCL) characterized by an indolent clinical course with slow progression over years from patches to plaques and eventually tumours. Nevertheless, the pathogenic mechanism implicated in this progression is not well understood. Micrornas (MiRNAS) are small noncoding RNAs that regulate the expression of multiple mRNAs and have a key role in the control of multiple biological processes implicated in cancer pathogenesis.
AIMS: Investigate the importance of miRNAs expression in MF progression.
Design: MATERIAL AND METHODS: Fifteen reactive cutaneous specimens and fourteen early MF-cutaneous samples were screened for miRNAs profiles. Early MF- patients exhibit a characteristic signature of 71 miRNAs (false discovery rate <0.05). The expression of 11 selected miRNAs were further studied by quantitative PCR in an additional series of 66 MFs (39 in plaque and 27 in tumoral stages, respectively) of whom 51 samples belonged to paired different stages of 16 patients.
Results: RESULTS: Bioinformatic analysis identified mir-26a, mir-222 and mir-146a as differentially expressed between MFs samples in early and advanced stages. Furthermore, statistical analysis in the sixteen patients with paired samples (plaque/tumoral) identified mir-181a and mir-146a differentially expressed. All these miRNAs have been implicated in the regulation of NF-KB, RAS, NOTCH, JAK-STAT and other signaling pathways implicated in MF progression. Moreover, mir-146a has been related to the development of either Treg or Th17 T-cells, by regulating the expression of both Foxp3 and NFATc1, respectively. Functional studies are being performed.
Conclusions: CONCLUSIONS: a signature of miRNAs targeting Treg and TH17 differentiation has been identified in the progression of CTCL samples.
Tuesday, March 5, 2013 2:15 PM
Proffered Papers: Section G, Tuesday Afternoon