Abstract:
:Non-small cell lung cancer (NSCLC) accounts for ∼80% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF-related apoptosis-inducing ligand (TRAIL) resistance in NSCLC cell lines, through the downregulation of p27(kip1), PTEN and TIMP3. Here, we further investigated this pathway and showed that miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in NSCLC cells through the c-Jun-mediated downregulation of miR-221 and miR-222. Moreover, we found that miR-130a reduced migratory capacity of NSCLC. A better understanding of MET-miR-221 and 222 axis regulation in drug resistance is the key in developing new strategies in NSCLC therapy.
journal_name
Oncogenejournal_title
Oncogeneauthors
Acunzo M,Visone R,Romano G,Veronese A,Lovat F,Palmieri D,Bottoni A,Garofalo M,Gasparini P,Condorelli G,Chiariello M,Croce CMdoi
10.1038/onc.2011.260subject
Has Abstractpub_date
2012-02-02 00:00:00pages
634-42issue
5eissn
0950-9232issn
1476-5594pii
onc2011260journal_volume
31pub_type
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