NAR cancerAug 27, 2026

SNHG family long RNAs help Ewing sarcoma cells grow by guiding small RNA changes in ribosomes

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Updated Aug 29, 2026

Abstract

Selective inhibition of SNHG1, SNHG12, and SNHG30 significantly reduced both proliferation of Ewing cells and the growth of Ewing tumors.

Over 90% of Ewing sarcomas are driven by the EWS-FLI1 fusion oncoprotein, which alters the expression of hundreds of genes.
The role of long non-coding RNAs (lncRNAs) in Ewing sarcoma oncogenesis is largely unknown.
Most lncRNA knockdowns had minimal effects on cell proliferation, except for SNHG1, SNHG12, and SNHG30.
Knockdown of SNHG1, SNHG12, and SNHG30 reduced Ewing cell proliferation in vitro and tumor growth in vivo.
A decrease in specific post-transcriptional modifications of rRNA was observed, linked to snoRNAs encoded by SNHG1 and SNHG12.
The study suggests that the expression of certain lncRNAs may be important for maintaining cancer cell fitness in Ewing sarcoma.

Simplified

Over 90% of Ewing sarcomas (EWS) are driven by the EWS-FLI1 fusion oncoprotein. EWS-FLI1 acts as a pioneer transcription factor, altering the expression of hundreds of genes including many long non-coding RNAs (lncRNAs). The role of these lncRNAs in the oncogenesis of EWS is mostly unknown. We developed a CRISPR interference (CRISPRi) strategy to knock down expression of lncRNA loci expressed in EWS and evaluate their effect on proliferation in vitro and tumor growth in vivo. While most lncRNA knockdown had minimal effect on cell proliferation, selective inhibition of SNHG1, SNHG12, and SNHG30 significantly reduced both proliferation of Ewing cells in vitro and the growth of Ewing tumors in vivo. These results were validated by individual knockdown followed by RNA-seq to assess their functional impact. We observed a decrease in post-transcriptional modifications (2'-O-methylation and pseudouridylation) at specific rRNA positions known to be guided by snoRNAs encoded in SNHG1 and SNHG12. Collectively, we demonstrate that expression of SNHG1, SNHG12, and SNHG30 in EWS cells contributes to the maintenance of cancer cell fitness via their role in intron-processed snoRNA genes. Thus, post-transcriptional regulation of rRNA may be a previously underappreciated consequence of EWS-FLI1 expression.

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SNHG family long RNAs help Ewing sarcoma cells grow by guiding small RNA changes in ribosomes

Abstract

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