LncRNA AC142119.1 facilitates the progression of neuroblastoma by epigenetically initiating the transcription of MYCN

• Published in: Journal of translational medicine 2023-09, Vol.21 (1), p.1-659, Article 659
• Main Authors: Yang, Rui, Liu, Nanjing, Li, Ting, Liu, Fangjie, Zhang, Jun, Zhao, Hui, Zou, Lin, He, Xiaoyan
• Format: Article
• Language: English
• Subjects: Analysis; Biological markers; Cancer; Care and treatment; Cell cycle; Cell growth; Cell lines; Cell proliferation; Chromatin; Development and progression; Electrophoretic mobility; Fluorescence in situ hybridization; Gene amplification; Gene expression; Genetic aspects; Genetic transcription; Hybridization; Immunoprecipitation; lncRNA AC142119.1; Mass spectrometry; Mass spectroscopy; Medical prognosis; MYCN; Neuroblastoma; Non-coding RNA; Proteins; Therapeutic targets; Transcription; Tumors; WDR5
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-023-04535-3

Background Oncogene MYCN is closely related with malignant progression and poor prognosis of neuroblastoma (NB). Recently, long non-coding RNAs (lncRNAs) have been recognized as crucial regulators in various cancers. However, whether lncRNAs contribute to the overexpression of MYCN in NB is unclear. Methods Microarray analysis were applied to analyze the differentially expressed lncRNAs between MYCN-amplified and MYCN-non-amplified NB cell lines. Bioinformatic analyses were utilized to identify lncRNAs nearby MYCN locus. qRT-PCR was used to detect the expression level of lncRNA AC142119.1 in NB cell lines and tissues. Gain- and loss-of-function assays were conducted to investigate the biological effect of AC142119.1 in NB. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation, mass spectrometry, RNA electrophoretic mobility shift, chromatin immunoprecipitation and chromatin isolation by RNA purification assays were performed to validate the interaction between AC142119.1 and WDR5 protein as well as MYCN promoter. Results AC142119.1 was significantly elevated in NB tissues with MYCN amplification, advanced INSS stage and high risk, and associated with poor survival of NB patients. Moreover, enforced expression of AC142119.1 reinforced the proliferation of NB cells in vitro and in vivo. Additionally, AC142119.1 specifically recruited WDR5 protein to interact with MYCN promoter, further initiating the transcription of MYCN and accelerating NB progression. Conclusions We identified a novel lncRNA AC142119.1, which promoted the progression of NB through epigenetically initiating the transcription of MYCN via interacting with both WDR5 protein and the promoter of MYCN, indicating that AC142119.1 might be a potential diagnostic biomarker and therapeutic target for NB. Keywords: Neuroblastoma, lncRNA AC142119.1, MYCN, WDR5