TY - JOUR
T1 - MiR-34a/c-Dependent PDGFR-α/β Downregulation Inhibits Tumorigenesis and Enhances TRAIL-Induced Apoptosis in Lung Cancer
AU - Garofalo, Michela
AU - Jeon, Young Jun
AU - Nuovo, Gerard J.
AU - Middleton, Justin
AU - Secchiero, Paola
AU - Joshi, Pooja
AU - Alder, Hansjuerg
AU - Nazaryan, Natalya
AU - Di Leva, Gianpiero
AU - Romano, Giulia
AU - Crawford, Melissa
AU - Nana-Sinkam, Patrick
AU - Croce, Carlo M.
PY - 2013/6/21
Y1 - 2013/6/21
N2 - Lung cancer is the leading cause of cancer mortality in the world today. Although some advances in lung cancer therapy have been made, patient survival is still poor. MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human malignancy. The miR-34 family consists of tumor-suppressive miRNAs, and its reduced expression has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we found that miR-34a and miR-34c target platelet-derived growth factor receptor alpha and beta (PDGFR-α and PDGFR-β), cell surface tyrosine kinase receptors that induce proliferation, migration and invasion in cancer. MiR-34a and miR-34c were downregulated in lung tumors compared to normal tissues. Moreover, we identified an inverse correlation between PDGFR-α/β and miR-34a/c expression in lung tumor samples. Finally, miR-34a/c overexpression or downregulation of PDGFR-α/β by siRNAs, strongly augmented the response to TNF-related apoptosis inducing ligand (TRAIL) while reducing migratory and invasive capacity of NSCLC cells.
AB - Lung cancer is the leading cause of cancer mortality in the world today. Although some advances in lung cancer therapy have been made, patient survival is still poor. MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human malignancy. The miR-34 family consists of tumor-suppressive miRNAs, and its reduced expression has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we found that miR-34a and miR-34c target platelet-derived growth factor receptor alpha and beta (PDGFR-α and PDGFR-β), cell surface tyrosine kinase receptors that induce proliferation, migration and invasion in cancer. MiR-34a and miR-34c were downregulated in lung tumors compared to normal tissues. Moreover, we identified an inverse correlation between PDGFR-α/β and miR-34a/c expression in lung tumor samples. Finally, miR-34a/c overexpression or downregulation of PDGFR-α/β by siRNAs, strongly augmented the response to TNF-related apoptosis inducing ligand (TRAIL) while reducing migratory and invasive capacity of NSCLC cells.
UR - https://www.scopus.com/pages/publications/84879267458
U2 - 10.1371/journal.pone.0067581
DO - 10.1371/journal.pone.0067581
M3 - Article
C2 - 23805317
AN - SCOPUS:84879267458
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e67581
ER -
