Language
English
Publication Date
1-16-2025
Journal
Journal of Experimental & Clinical Cancer Research
DOI
10.1186/s13046-025-03278-x
PMID
39815331
PMCID
PMC11737211
PubMedCentral® Posted Date
1-16-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Emerging evidence shows that small nucleolar RNA (snoRNA), a type of highly conserved non-coding RNA, is involved in tumorigenesis and aggressiveness. However, the roles of snoRNAs in regulating alternative splicing crucial for cancer progression remain elusive.
Methods: High-throughput RNA sequencing and comprehensive analysis were performed to identify crucial snoRNAs and downstream alternative splicing events. Biotin-labeled RNA pull-down, mass spectrometry, cross-linking RNA immunoprecipitation, and in vitro binding assays were applied to explore interaction of snoRNAs with protein partners. Alternative splicing and gene expression was observed by real-time quantitative RT-PCR and western blot assays. In vitro and in vivo studies were performed to investigate biological effects of snoRNAs and their protein partners in gastric cancer. Survival analysis was undertaken by using Kaplan-Meier method and log-rank test.
Results: SNORA37 was identified as an up-regulated snoRNA essential for tumorigenesis and aggressiveness of gastric cancer. Gain- and loss-of-function studies indicated that SNORA37 promoted the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. Mechanistically, as an ELAV like RNA binding protein 1 (ELAVL1)-generated snoRNA, SNORA37 directly bound to cap methyltransferase 1 (CMTR1) to facilitate its interaction with ELAVL1, resulting in nuclear retention and activity of ELAVL1 in regulating alternative splicing of CD44. Rescue studies revealed that SNORA37 exerted oncogenic roles in gastric cancer progression via facilitating CMTR1-ELAVL1 interaction. In clinical gastric cancer cases, high levels of SNORA37, CMTR1, ELAVL1, or CD44 were associated with shorter survival and poor outcomes of patients.
Conclusions: These results indicated that SNORA37/CMTR1/ELAVL1 feedback loop drives gastric cancer progression via facilitating CD44 alternative splicing.
Keywords
Stomach Neoplasms, Humans, ELAV-Like Protein 1, Alternative Splicing, Hyaluronan Receptors, Animals, Mice, Disease Progression, RNA, Small Nucleolar, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Mice, Nude, Female, Cell Proliferation, Male, Small nucleolar RNA, Cap methyltransferase 1, ELAV like RNA binding protein 1, Alternative splicing, Cancer progression
Published Open-Access
yes
Recommended Citation
Bao, Banghe; Tian, Minxiu; Wang, Xiaojing; et al., "SNORA37/CMTR1/ELAVL1 Feedback Loop Drives Gastric Cancer Progression via Facilitating CD44 Alternative Splicing" (2025). Faculty, Staff and Students Publications. 8270.
https://digitalcommons.library.tmc.edu/baylor_docs/8270