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Updated: Jan 25, 2026

Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data
Published on: December 1, 2023
The Promoter-Associated Noncoding RNA pncCCND1_B Assembles a Protein-RNA Complex to Regulate Cyclin D1 Transcription
Ramona Palombo1, Paola Frisone1, Marco Fidaleo1
1Laboratory of Cellular and Molecular Neurobiology, Fondazione Santa Lucia, Via del Fosso di Fiorano, Rome, Italy.
Abstract:
Most Ewing sarcomas are characterized by the in-frame chromosomal translocation t(11;22) generating the EWS-FLI1 oncogene. EWS-FLI1 protein interacts with the RNA helicase DHX9 and affects transcription and processing of genes involved in neoplastic transformation, including CCND1 (the cyclin D1 gene), which contributes to cell-cycle dysregulation in cancer. In this study, we found that CCND1 expression is significantly higher in patients with Ewing sarcoma compared with other sarcomas and that the pncCCND1_B RNA, a previously uncharacterized CCND1 promoter-associated noncoding (pnc) transcript, is expressed in Ewing sarcoma cells. PncCCND1_B interacted with the RNA-binding protein Sam68 and repressed CCND1 expression. Notably, knockdown of Sam68 affected pncCCND1_B subcellular localization and cyclin D1 expression. Pharmacologic impairment of DHX9/EWS-FLI1 interaction promoted RNA-dependent association of Sam68 with DHX9 and recruitment of Sam68 to the CCND1 promoter, thus repressing it. Conversely, mitogenic stimulation of Ewing sarcoma cells with IGF1 impaired Sam68/DHX9 interaction and positively regulated CCND1 expression. These studies uncover a fine-tuned modulation of the proto-oncogene CCND1 in Ewing sarcoma cells via alternative complexes formed by DHX9 with either EWS-FLI1 or pncCCND1_B-Sam68. SIGNIFICANCE: A pncRNA-based mechanism represses expression of CCND1 through the formation of a protein-RNA complex and provides new therapeutic opportunities for patients with Ewing sarcoma.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/14/3570/F1.large.jpg.
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