Language
English
Publication Date
11-23-2023
Journal
Journal of Experimental & Clinical Cancer Research
DOI
10.1186/s13046-023-02898-5
PMID
37993881
PMCID
PMC10666356
PubMedCentral® Posted Date
11-23-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Recent evidence reveals the emerging functions of circular RNA (circRNA) and protein glycosylation in cancer progression. However, the roles of circRNA in regulating glycosyltransferase expression in gastric cancer remain to be determined.
Methods: Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by chromatin immunoprecipitation, RNA immunoprecipitation, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its partners on the glycosylation, growth, invasion, and metastasis of gastric cancer cells.
Results: Circ-hnRNPU, an exonic circRNA derived from heterogenous nuclear ribonuclear protein U (hnRNPU), was identified to exert tumor suppressive roles in protein glycosylation and progression of gastric cancer. Mechanistically, circ-hnRNPU physically interacted with non-POU domain containing octamer binding (NONO) protein to induce its cytoplasmic retention, resulting in down-regulation of glycosyltransferases (GALNT2, GALNT6, MGAT1) and parental gene hnRNPU via repression of nuclear NONO-mediated c-Myc transactivation or cytoplasmic NONO-facilitated mRNA stability. Rescue studies indicated that circ-hnRNPU inhibited the N- and O-glycosylation, growth, invasion, and metastasis of gastric cancer cells via interacting with NONO protein. Pre-clinically, administration of lentivirus carrying circ-hnRNPU suppressed the protein glycosylation, tumorigenesis, and aggressiveness of gastric cancer xenografts. In clinical cases, low circ-hnRNPU levels and high NONO or c-Myc expression were associated with poor survival outcome of gastric cancer patients.
Conclusions: These findings indicate that circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.
Keywords
Humans, Cell Line, Tumor, Cell Proliferation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Glycosylation, MicroRNAs, Nuclear Proteins, RNA, Circular, RNA, Messenger, RNA-Binding Proteins, Stomach Neoplasms, Transcription Factors, Transcriptional Activation, Heterogeneous-Nuclear Ribonucleoprotein U, Gastric cancer, Circular RNA, Heterogenous nuclear ribonuclear protein U, Non-POU domain containing octamer binding, Glycosylation
Published Open-Access
yes
Recommended Citation
Li, Hongjun; Jiao, Wanju; Song, Jiyu; et al., "Circ-hnRNPU Inhibits Nono-Mediated C-Myc Transactivation and mRNA Stabilization Essential for Glycosylation and Cancer Progression" (2023). Faculty, Staff and Students Publications. 8273.
https://digitalcommons.library.tmc.edu/baylor_docs/8273