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SNORA37/CMTR1/ELAVL1 feedback loop drives gastric cancer progression via facilitating CD44 alternative splicing

Banghe Bao1, Minxiu Tian1, Xiaojing Wang2,3

  • 1Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, People's Republic of China.

Journal of Experimental & Clinical Cancer Research : CR
|January 15, 2025
PubMed
Abstract

Insights

Small nucleolar RNA SNORA37 drives gastric cancer by regulating CD44 alternative splicing through the CMTR1-ELAVL1 feedback loop, impacting patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • RNA Biology

Background:

  • Small nucleolar RNAs (snoRNAs) are increasingly implicated in cancer development and progression.
  • The specific roles of snoRNAs in regulating alternative splicing, a key process in cancer, are not fully understood.

Purpose of the Study:

  • To identify key snoRNAs involved in gastric cancer progression.
  • To elucidate the molecular mechanisms by which snoRNAs regulate alternative splicing in gastric cancer.
  • To investigate the clinical significance of identified snoRNAs and their associated pathways.

Main Methods:

  • High-throughput RNA sequencing to identify dysregulated snoRNAs and alternative splicing events.
  • RNA pull-down, mass spectrometry, and immunoprecipitation assays to determine snoRNA-protein interactions.
  • In vitro and in vivo functional studies, RT-qPCR, and western blotting to assess biological effects.
  • Survival analysis using Kaplan-Meier method and log-rank test on clinical samples.

Main Results:

  • SNORA37 was identified as a significantly upregulated snoRNA in gastric cancer, promoting tumor growth, invasion, and metastasis.
  • SNORA37 directly interacts with CMTR1, facilitating its association with ELAVL1, thereby enhancing ELAVL1-mediated CD44 alternative splicing.
  • High expression of SNORA37, CMTR1, ELAVL1, or CD44 correlated with poor patient survival and adverse outcomes in gastric cancer.

Conclusions:

  • A novel SNORA37/CMTR1/ELAVL1 feedback loop promotes gastric cancer progression.
  • This loop drives tumorigenesis by facilitating CD44 alternative splicing.
  • Targeting this pathway may offer therapeutic strategies for gastric cancer.
Keywords:
Alternative splicingCancer progressionCap methyltransferase 1ELAV like RNA binding protein 1Small nucleolar RNA

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