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snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review)

  • Authors:
    • Jiahui Mao
    • Hao Lin
    • Feng Gu
    • Zhaoji Pan
  • View Affiliations / Copyright

    Affiliations: Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212008, P.R. China, Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Southeast University, Xuzhou, Jiangsu 221009, P.R. China, Department of Clinical Laboratory, Xuzhou Central Hospital, Southeast University, Xuzhou, Jiangsu 221009, P.R. China
    Copyright: © Mao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 80
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    Published online on: May 15, 2026
       https://doi.org/10.3892/ijo.2026.5893
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Abstract

Small nucleolar RNAs (snoRNAs) are a conserved class of non‑coding RNAs that guide 2'‑O‑methylation and pseudouridylation of ribosomal RNA. First identified over five decades ago, snoRNAs have emerged as critical regulators of cellular function, with high‑throughput sequencing revealing their dysregulation in numerous human diseases, particularly cancer. In the present review, the biogenesis, classification, and modification mechanisms of snoRNAs and snoRNA‑derived fragments (sdRNAs) are comprehensively summarized. Recent advances in understanding their non‑canonical functions are highlighted, which extend beyond ribosomal RNA modification to include regulation of mRNA splicing, stability, and protein interactions. These diverse mechanisms enable snoRNAs to influence key cancer‑related processes such as proliferation, metastasis, metabolic reprogramming, and therapy resistance. A comprehensive overview of snoRNA dysregulation across major cancer types is provided, including colorectal, hepatocellular, gastric, lung, breast, and ovarian cancers, with a detailed discussion of underlying molecular pathways. Furthermore, their emerging potential as diagnostic and prognostic biomarkers detectable in liquid biopsies is examined, as well as their promise as therapeutic targets amenable to antisense oligonucleotide and small molecule intervention. The present review integrates current knowledge of snoRNA/sdRNA biology and highlights critical gaps and future directions, providing a foundation for translating these regulatory RNAs into clinical oncology applications.
View Figures

Figure 1

Characterization, biogenesis and
canonical function of snoRNAs. (A) Genomic organization of snoRNAs:
Intronic snoRNAs are processed from host gene transcripts, while
some snoRNAs are transcribed from independent promoters. (B)
Structural features of C/D box and H/ACA box snoRNAs and canonical
functions: Showing conserved motifs (C/D boxes, H/ACA domains) and
core binding proteins (fibrillarin and dyskerin). C/D box snoRNAs
guide 2'-O-methylation of rRNA and snRNA; H/ACA box snoRNAs guide
pseudouridylation. (C) Biogenesis pathway: snoRNAs associate with
core proteins to form snoRNPs, are transported to Cajal bodies for
maturation, and localize to nucleoli. snoRNA, small nucleolar RNA;
rRNA, ribosomal RNA; snRNA, small nuclear RNA; snoRNP, small
nucleolar ribonucleoprotein; mRNA, messenger RNA; tRNA transfer
RNA.

Figure 2

Biogenesis and function of sdRNAs.
(A) Processing pathways of C/D box snoRNA-derived fragments. C/D
box snoRNAs are processed via DGCR8-dependent or independent
pathways to yield longer (>26 nt) and shorter (17-19 nt)
fragments from the 5' end, which may adopt piRNA-like or miRNA-like
functions. (B) Functional outcomes of sdRNAs. miRNA-like sdRNAs
associate with AGO proteins and silence target mRNAs; piRNA-like
sdRNAs bind PIWI proteins and regulate gene expression
epigenetically; siRNA-like sdRNAs guide transcript cleavage through
near-perfect complementarity. In addition, both full-length snoRNAs
and specific sdRNAs have been implicated in the regulation of
pre-mRNA alternative splicing (such as SNORD115 and SNORD88C),
expanding their regulatory repertoire beyond RNA modification and
gene silencing. (C) Processing pathways of H/ACA box snoRNA-derived
fragments. H/ACA box snoRNAs are processed by DICER to generate
20-24 nt fragments predominantly from the 3' terminus, which can
function as miRNA-like molecules. Representative examples from each
category are indicated. snoRNA, small nucleolar RNA; sdRNA,
snoRNA-derived fragments; DGCR8, DiGeorge syndrome critical region
8; AGO, Argonaute; PIWI, P-element-induced wimpy testis; piRNA,
PIWI-interacting RNA; miRNA, microRNA; siRNA, small interfering
RNA; DICER, ribonuclease III Dicer; SNORD, C/D box snoRNA.

Figure 3

Representative examples highlighting
the cross-cancer clinical implications of snoRNAs. (A) snoRNAs as
diagnostic biomarkers: Emphasizing their cross-cancer applicability
in liquid biopsies for non-invasive detection (such as SNORA51 in
fecal samples for CRC, and SNORD33 in plasma for TNBC). (B) snoRNAs
as prognostic biomarkers: Highlighting their conserved roles in
driving shared oncogenic phenotypes, such as tumor proliferation,
cell-cycle dysregulation, and invasion/metastasis, where the
elevated expression of oncogenic snoRNAs (such as SNORA28 in CRC,
and SNORD17 in HCC) consistently correlates with advanced TNM
staging and poor overall survival across diverse malignancies. (C)
snoRNAs as therapeutic targets: Demonstrating the pan-cancer
potential of targeted interventions, where ASOs directed against
key oncogenic snoRNAs (such as SNORD17, and SNORA74A) effectively
suppress tumor growth and metastatic progression in preclinical
models. This figure presents selected representative examples
rather than an exhaustive overview to illustrate broader pan-cancer
themes. snoRNA, small nucleolar RNA; CRC, colorectal cancer; SNORD,
C/D box snoRNA; TNBC, triple-negative breast cancer; HCC,
hepatocellular carcinoma; ASO, antisense oligonucleotide; SNORA,
H/ACA box snoRNA; NSCLC, non-small cell lung cancer; BC, breast
cancer; ESCA, esophageal carcinoma; OC, ovarian cancer; EC,
endometrial cancer; PDAC, pancreatic ductal adenocarcinoma.
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Copy and paste a formatted citation
Spandidos Publications style
Mao J, Lin H, Gu F and Pan Z: snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review). Int J Oncol 69: 80, 2026.
APA
Mao, J., Lin, H., Gu, F., & Pan, Z. (2026). snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review). International Journal of Oncology, 69, 80. https://doi.org/10.3892/ijo.2026.5893
MLA
Mao, J., Lin, H., Gu, F., Pan, Z."snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review)". International Journal of Oncology 69.1 (2026): 80.
Chicago
Mao, J., Lin, H., Gu, F., Pan, Z."snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review)". International Journal of Oncology 69, no. 1 (2026): 80. https://doi.org/10.3892/ijo.2026.5893
Copy and paste a formatted citation
x
Spandidos Publications style
Mao J, Lin H, Gu F and Pan Z: snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review). Int J Oncol 69: 80, 2026.
APA
Mao, J., Lin, H., Gu, F., & Pan, Z. (2026). snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review). International Journal of Oncology, 69, 80. https://doi.org/10.3892/ijo.2026.5893
MLA
Mao, J., Lin, H., Gu, F., Pan, Z."snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review)". International Journal of Oncology 69.1 (2026): 80.
Chicago
Mao, J., Lin, H., Gu, F., Pan, Z."snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review)". International Journal of Oncology 69, no. 1 (2026): 80. https://doi.org/10.3892/ijo.2026.5893
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