Long noncoding RNA ZFAS1 promoting small nucleolar RNA-mediated 2′-O-methylation via NOP58 recruitment in colorectal cancer

• DOI: 10.1186/s12943-020-01201-w
• Publication Date: 2020-05-22T06:02:46Z
• Authors: Huizhe Wu; Wenyan Qin; Senxu Lu; Xiufang Wang; Jing Zhang; Tong Sun; Xiaoyun Hu; Yalun Li; Qiuchen Chen; Yuanhe Wang; Haishan Zhao; Haiyan Piao; Rui Zhang; Minjie Wei
• Keywords: Small nucleolar RNA

Abstract Background Increasing evidence supports the role of small nucleolar RNAs (snoRNAs) and long non-coding (lncRNAs) as master gene regulators at epigenetic modification level. However, underlying mechanism these functional ncRNAs in colorectal cancer (CRC) has not been well investigated. Methods The dysregulated expression profiling lncRNAs-snoRNAs-mRNAs their correlations co-expression enrichment were assessed by GeneChip microarray analysis. candidate lncRNAs, snoRNAs, target genes detected situ hybridization (ISH), RT-PCR, qPCR immunofluorescence (IF) assays. biological functions factors investigated using vitro vivo studies that included CCK8, trans-well, cell apoptosis, IF assay, western blot method, xenograft mice models. rRNA 2′-O-methylation (Me) activities determined RTL-P assay a novel double-stranded primer based on single-stranded toehold (DPBST) assay. molecular mechanisms explored bioinformatics RNA stability, fluorescence ISH, pull-down translation inhibition Results To demonstrate involvement lncRNA snoRNAs 2′-O-Me during tumorigenesis, we uncovered previously unreported linking snoRNPs NOP58 regulated ZFAS1 control SNORD12C, SNORD78 mediated CRC initiation development. Specifically, exerts its oncogenic significantly up-regulated accompanied elevated NOP58, SNORD12C/78 cells tissues. knockdown suppressed proliferation, migration, increased this inhibitory effect could be reversed overexpression vivo. Mechanistically, protein recognized specific motif (AAGA or CAGA) ZFAS1. This event accelerates assembly to allow for further guiding corresponding Gm3878 Gm4593 sites. Importantly, silencing SNORD12C 78 reduced rRNAs activities, which rescued ZFAS1, subsequently inhibits stability activity downstream targets (e.g., EIF4A3 LAMC2). Conclusion ZFAS1-NOP58-SNORD12C/78-EIF4A3/LAMC2 signaling axis tumorigenesis provides better understanding regarding lncRNA-snoRNP-mediated prevention treatment CRC.