DOI . ORG {
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We began analyzing https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003996, but it redirected us to https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003996. The analysis below is for the second page.
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Author Summary The MYCN oncogene has a central role in the genesis and progression of neuroblastomas, and its amplification is associated with an unfavorable prognosis. We have found that NCYM, a MYCN cis-antisense RNA, is translated in humans to a de novo evolved protein. NCYM inhibits GSK3β to stabilize MYCN, whereas MYCN induces NCYM transcription. The positive feedback regulation formed in the MYCN/NCYM-amplified tumors promotes the aggressive nature of human neuroblastoma. MYCN transgenic mice, which express human MYCN in sympathoadrenal tissues, spontaneously develop neuroblastomas. However, unlike human neuroblastoma, distant metastasis is infrequent. We established MYCN/NCYM double transgenic mice as a new animal model for studying neuroblastoma pathogenesis. We found that NCYM expression promoted both the metastasis and chemo-resistance of the neuroblastomas formed in the double transgenic mice. These results demonstrate that NCYM may be a potential target for developing novel therapeutic tools against high-risk neuroblastomas in humans, and that the MYCN/NCYM double transgenic mouse may be a suitable model for the screening of these new drugs.
Title[redir]:
No title found...
Description:
Author Summary The MYCN oncogene has a central role in the genesis and progression of neuroblastomas, and its amplification is associated with an unfavorable prognosis. We have found that NCYM, a MYCN cis-antisense RNA, is translated in humans to a de novo evolved protein. NCYM inhibits GSK3β to stabilize MYCN, whereas MYCN induces NCYM transcription. The positive feedback regulation formed in the MYCN/NCYM-amplified tumors promotes the aggressive nature of human neuroblastoma. MYCN transgenic mice, which express human MYCN in sympathoadrenal tissues, spontaneously develop neuroblastomas. However, unlike human neuroblastoma, distant metastasis is infrequent. We established MYCN/NCYM double transgenic mice as a new animal model for studying neuroblastoma pathogenesis. We found that NCYM expression promoted both the metastasis and chemo-resistance of the neuroblastomas formed in the double transgenic mice. These results demonstrate that NCYM may be a potential target for developing novel therapeutic tools against high-risk neuroblastomas in humans, and that the MYCN/NCYM double transgenic mouse may be a suitable model for the screening of these new drugs.
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Keywords {🔍}
mycn, ncym, human, neuroblastoma, cells, figure, expression, mice, protein, transgenic, gene, article, cell, view, neuroblastomas, google, scholar, mycnncym, gskβ, mrna, tumors, novo, double, levels, primary, mouse, promoter, genes, plos, number, httpsdoiorgjournalpgens, survival, tumor, tif, evolved, activity, tissues, purified, cancer, analysis, sequences, measured, chp, assay, signaling, mycnamplified, antibody, test, region, knockdown,
Topics {✒️}
health computational data analyses plos genet 10 plos genet 3 plos genet 7 plos genet 8 contributed reagents/materials/analysis tools cookies plos quantitative real-time rt-pcr cdk1 complex plays gst-fused cdk1/cyclin b1 global coe program monte-carlo chi-square test ncym-luc e-box mt open-access article distributed medicine diseases ncym-luc e-box wt global center pgex-4t-ncym plasmid e-box-dependent manner purified cdk1/cyclin b1 chi-square independence test taxonomically-restricted genes important mycn/ncym-amplified tumors promotes intact upstream e-box putative e-boxes exist putative e-box sequence cleaved caspase-3–positive areas 129/svj×c57bl/6j mice putative e-box located kaplan–meier survival curves ncym knockdown-mediated destabilization original author chi-squared statistic normalized mycn cis-antisense rna protein g-sepharose beads chemiluminescence-based detection kit mtor-dependent feedback inhibition pi3k/mtor-dual inhibitor proteasome-dependent protein degradation gst-tag cleavage mediated kaplan–meier survival analysis n-cym1 custom shrna human protein-coding genes full-length ncym protein mycn/ncym transgenic mice polyclonal anti-ncym antibody complex mycn/ncym transgenic mouse
Questions {❓}
- Khalturin K, Hemmrich G, Fraune S, Augustin R, Bosch TC (2009) More than just orphans: are taxonomically-restricted genes important in evolution?
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