SNORD11B-mediated 2′-O-methylation of primary let-7a in colorectal carcinogenesis

Evidence indicates that small nucleolar RNAs (snoRNAs) participate in tumorigenesis and development and could be promising biomarkers for colorectal cancer (CRC). Here, we examine the profile of snoRNAs in CRC and find that expression of SNORD11B is increased in CRC tumor tissues and cell lines, wit...

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Bibliographic Details
Published in:Oncogene 2023-10, Vol.42 (41), p.3035-3046
Main Authors: Bian, Zhixuan, Xu, Chang, Xie, Yi, Wang, Xiaoying, Chen, Yan, Mao, Siwei, Wu, Qi, Zhu, Jiabei, Huang, Nan, Zhang, Yue, Ma, Ji, Sun, Fenyong, Pan, Qiuhui
Format: Article
Language:English
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Antigens
Apoptosis
Biomarkers
Carcinogenesis
Cell Biology
Cell proliferation
Chromosome 5
Chromosomes
Colorectal cancer
Colorectal carcinoma
Cytoplasm
Genes
Human Genetics
Internal Medicine
Laboratories
Localization
Lymph nodes
Medical prognosis
Medicine
Medicine & Public Health
Metastases
MicroRNAs
Nucleoli
Oncology
Proteins
Ribonucleic acid
RNA
rRNA
Tumor cell lines
Tumor suppressor genes
Tumorigenesis
Tumors
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Summary:Evidence indicates that small nucleolar RNAs (snoRNAs) participate in tumorigenesis and development and could be promising biomarkers for colorectal cancer (CRC). Here, we examine the profile of snoRNAs in CRC and find that expression of SNORD11B is increased in CRC tumor tissues and cell lines, with a significant positive correlation between SNORD11B expression and that of its host gene NOP58. SNORD11B promotes CRC cell proliferation and invasion and inhibits apoptosis. Mechanistically, SNORD11B promotes the processing and maturation of 18 S ribosomal RNA (rRNA) by mediating 2’-O-methylated (Nm) modification on the G509 site of 18 S rRNA. Intriguingly, SNORD11B mediates Nm modification on the G225 site of MIRLET7A1HG (pri-let-7a) with a canonical motif, resulting in degradation of pri-let-7a, inhibition of DGCR8 binding, reduction in mature tumor suppressor gene let-7a-5p expression, and upregulation of downstream oncogene translation. SNORD11B performs comparably to CEA and CA199 in diagnosing CRC. High expression of SNORD11B is significantly correlated with a more advanced TNM stage and lymph node metastasis, which indicates poor prognosis.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-023-02808-1