dc.contributor.author | O'Brien, EM | |
dc.contributor.author | Selfe, JL | |
dc.contributor.author | Martins, AS | |
dc.contributor.author | Walters, ZS | |
dc.contributor.author | Shipley, JM | |
dc.date.accessioned | 2018-07-31T10:47:09Z | |
dc.date.issued | 2018-02-21 | |
dc.identifier.citation | BMC cancer, 2018, 18 (1), pp. 217 - ? | |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2227 | |
dc.identifier.eissn | 1471-2407 | |
dc.identifier.doi | 10.1186/s12885-018-4129-8 | |
dc.description.abstract | BACKGROUND: MYCN is amplified in small cell lung cancers and several pediatric tumors, including alveolar rhabdomyosarcomas and neuroblastomas. MYCN protein is known to play a key oncogenic role in both alveolar rhabdomyosarcomas and neuroblastomas. MYCN opposite strand (MYCNOS) is a gene located on the antisense strand to MYCN that encodes alternatively spliced transcripts, two of which (MYCNOS-01 and MYCNOS-02) are known to be expressed in neuroblastoma and small cell lung cancer with reciprocal regulation between MYCNOS-02 and MYCN reported for neuroblastomas. We sought to determine a functional role for MYCNOS-01 in alveolar rhabdomyosarcoma and neuroblastoma cells and identify any associated regulatory effects between MYCN and MYCNOS-01. METHODS: MYCNOS-01, MYCNOS-02 and MYCN expression levels were assessed in alveolar rhabdomyosarcoma and neuroblastoma cell lines and tumor samples from patients using Affymetrix microarray data and quantitative RT-PCR. Following MYCNOS-01 or MYCN siRNA knockdown and MYCNOS-01 overexpression, transcript levels were assayed by quantitative RT-PCR and MYCN protein expression assessed by Western blot and immunofluorescence. Additionally, effects on cell growth, apoptosis and cell cycle profiles were determined by a metabolic assay, caspase activity and flow cytometry, respectively. RESULTS: MYCNOS-01 transcript levels were generally higher in NB and RMS tumor samples and cell lines with MYCN genomic amplification. RNA interference of MYCNOS-01 expression did not alter MYCN transcript levels but decreased MYCN protein levels. Conversely, MYCN reduction increased MYCNOS-01 transcript levels, creating a negative feedback loop on MYCN protein levels. Reduction of MYCNOS-01 or MYCN expression decreased cell growth in MYCN-amplified alveolar rhabdomyosarcoma and neuroblastoma cell lines. This is consistent with MYCNOS-01-mediated regulation of MYCN contributing to the phenotype observed. CONCLUSIONS: An alternative transcript of MYCNOS, MYCNOS-01, post-transcriptionally regulates MYCN levels and affects growth in MYCN-amplified rhabdomyosarcoma and neuroblastoma cells. | |
dc.format | Electronic | |
dc.format.extent | 217 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BIOMED CENTRAL LTD | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Rhabdomyosarcoma, Alveolar | |
dc.subject | Neuroblastoma | |
dc.subject | Apoptosis | |
dc.subject | Cell Proliferation | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | RNA, Long Noncoding | |
dc.subject | N-Myc Proto-Oncogene Protein | |
dc.title | The long non-coding RNA MYCNOS-01 regulates MYCN protein levels and affects growth of MYCN-amplified rhabdomyosarcoma and neuroblastoma cells. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-02-13 | |
rioxxterms.versionofrecord | 10.1186/s12885-018-4129-8 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-02-21 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | BMC cancer | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology | |
pubs.publication-status | Published | |
pubs.volume | 18 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Sarcoma Molecular Pathology | |
dc.contributor.icrauthor | O'Brien, Eleanor | |
dc.contributor.icrauthor | Selfe, Joanna | |
dc.contributor.icrauthor | Shipley, Janet | |