期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 61, 期 14, 页码 -出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.61.14.8
关键词
retinoblastoma; MYCN; long noncoding RNA MYCNOS1; RB1; photoreceptor signature; drug response
资金
- Commission on Higher Education [MRG6280083]
- Faculty of Medicine, Ramathibodi Hospital [CF_60002]
- Mahidol University
- Thailand Research Fund
PURPOSE. MYCNOS (MYCN opposite strand) is co-amplified with MYCN in pediatric cancers, including retinoblastoma. MYCNOS encodes several RNA variants whose functions have not been elucidated in retinoblastoma. Thus, we attempted to identify MYCNOS variants in retinoblastoma and aimed to decipher the role of MYCNOS variant 1 (MYCNOS1) on the activity of MYCN-amplified retinoblastoma. METHODS. The profiles of MYCNOS variants and MYCN status were determined in 17 retinoblastoma tissues, cell lines, retinas, and retinal organoids. A functional study of MYCNOS1 expression was conducted in patient-derived tumor cells and in retinoblastoma cell lines via short hairpin RNA-mediated gene silencing. We carried out MYCN expression, cell viability, cell cycle, apoptosis, soft agar colony formation, and transwell assays to examine the role of MYCNOS1 in MYCN and cell behaviors. We analyzed a transcriptome of MYCN-amplified retinoblastoma cells deficient for MYCNOS1 and, finally, tested the responses of these cells to chemotherapeutic agents. RESULTS. Expression of MYCNOS1 was associated with the expression and copy number of MYCN. Knockdown of MYCNOS1 caused instability of the MYCN protein, leading to cell cycle arrest and impaired proliferation and chemotaxis-directed migration in MYCNamplified retinoblastoma cells in which RB1 was intact. MYCNOS1 expression was associated with gene signatures of photoreceptor cells and epithelial-mesenchymal transition. MYCNOS1 silencing enhanced the response of retinoblastoma cells to topotecan but not carboplatin. CONCLUSIONS. MYCNOS1 supports progression of retinoblastoma. Inhibition of MYCNOS1 expression may be necessary to suppress MYCN activity when treating MYCN-amplified cancers without RB1 mutation.
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