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dc.contributor.authorJoshi, P
dc.contributor.authorJeon, Y
dc.contributor.authorLaganà, A
dc.contributor.authorMiddleton, J
dc.contributor.authorSecchiero, P
dc.contributor.authorGarofalo, Michela
dc.contributor.authorCroce, C
dc.date.accessioned2015-07-23T15:45:58Zen
dc.date.available2015-07-23T15:45:58Zen
dc.date.issued2015-07-14en
dc.identifier.citationMicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC. 2015, 112 (28):8650-5 Proc Natl Acad Sci USAen
dc.identifier.issn1091-6490en
dc.identifier.pmid26124099en
dc.identifier.doi10.1073/pnas.1500886112en
dc.identifier.urihttp://hdl.handle.net/10541/560922en
dc.description.abstractNonsmall cell lung cancer (NSCLC) is one of the leading causes of death worldwide. TNF-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in malignant cells without inducing significant toxicity in normal cells. However, several carcinomas, including lung cancer, remain resistant to TRAIL. MicroRNAs (miRNAs) are small noncoding RNAs of ∼24 nt that block mRNA translation and/or negatively regulate its stability. They are often aberrantly expressed in cancer and have been implicated in increasing susceptibility or resistance to TRAIL-induced apoptosis by inhibiting key functional proteins. Here we show that miR-148a is down-regulated in cells with acquired TRAIL-resistance compared with TRAIL-sensitive cells. Enforced expression of miR-148a sensitized cells to TRAIL and reduced lung tumorigenesis in vitro and in vivo through the down-modulation of matrix metalloproteinase 15 (MMP15) and Rho-associated kinase 1 (ROCK1). These findings suggest that miR-148a acts as a tumor suppressor and might have therapeutic application in the treatment of NSCLC.
dc.language.isoenen
dc.rightsArchived with thanks to Proceedings of the National Academy of Sciences of the United States of Americaen
dc.titleMicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC.en
dc.typeArticleen
dc.contributor.departmentDepartment of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OHen
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen
html.description.abstractNonsmall cell lung cancer (NSCLC) is one of the leading causes of death worldwide. TNF-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in malignant cells without inducing significant toxicity in normal cells. However, several carcinomas, including lung cancer, remain resistant to TRAIL. MicroRNAs (miRNAs) are small noncoding RNAs of ∼24 nt that block mRNA translation and/or negatively regulate its stability. They are often aberrantly expressed in cancer and have been implicated in increasing susceptibility or resistance to TRAIL-induced apoptosis by inhibiting key functional proteins. Here we show that miR-148a is down-regulated in cells with acquired TRAIL-resistance compared with TRAIL-sensitive cells. Enforced expression of miR-148a sensitized cells to TRAIL and reduced lung tumorigenesis in vitro and in vivo through the down-modulation of matrix metalloproteinase 15 (MMP15) and Rho-associated kinase 1 (ROCK1). These findings suggest that miR-148a acts as a tumor suppressor and might have therapeutic application in the treatment of NSCLC.


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