TY - JOUR
T1 - Epigenetic silencing of miR-145-5p contributes to brain metastasis
AU - Donzelli, Sara
AU - Mori, Federica
AU - Bellissimo, Teresa
AU - Sacconi, Andrea
AU - Casini, Beatrice
AU - Frixa, Tania
AU - Roscilli, Giuseppe
AU - Aurisicchio, Luigi
AU - Facciolo, Francesco
AU - Pompili, Alfredo
AU - Carosi, Maria Antonia
AU - Pescarmona, Edoardo
AU - Segatto, Oreste
AU - Pond, Greg
AU - Muti, Paola
AU - Telera, Stefano
AU - Strano, Sabrina
AU - Yarden, Yosef
AU - Blandino, Giovanni
N1 - This work was supported by AIRC to GB (AIRC 14455) and EPIGEN to GB (13/05/R/42).
PY - 2015/11/3
Y1 - 2015/11/3
N2 - Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.
AB - Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.
UR - http://www.scopus.com/inward/record.url?scp=84946893445&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.5930
DO - 10.18632/oncotarget.5930
M3 - مقالة
SN - 1949-2553
VL - 6
SP - 35183
EP - 35201
JO - Oncotarget
JF - Oncotarget
IS - 34
ER -