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

Zhixuan Bian; Chang Xu; Yi Xie; Xiaoying Wang; Yan Chen; Siwei Mao; Qi Wu; Jiabei Zhu; Nan Huang; Yue Zhang; Ji Ma; Fenyong Sun; Qiuhui Pan

doi:10.1038/s41388-023-02808-1

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

Oncogene. 2023 Oct;42(41):3035-3046. doi: 10.1038/s41388-023-02808-1. Epub 2023 Aug 24.

Authors

Zhixuan Bian^#^{1

2

3

4}, Chang Xu^#⁵, Yi Xie^#^{1

2

3}, Xiaoying Wang⁵, Yan Chen⁵, Siwei Mao^{1

2

3}, Qi Wu⁵, Jiabei Zhu^{1

2

3}, Nan Huang⁵, Yue Zhang⁶, Ji Ma^{1

2

3}, Fenyong Sun⁷, Qiuhui Pan^{8

9

10

11}

Affiliations

¹ Department of Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
² College of Health Science and Technology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
³ Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai, 200127, China.
⁴ Department of Laboratory Medicine, Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center, Sanya, 572000, China.
⁵ Department of Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
⁶ Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
⁷ Department of Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China. sunfenyong@263.net.
⁸ Department of Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. panqiuhui@scmc.com.cn.
⁹ College of Health Science and Technology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. panqiuhui@scmc.com.cn.
¹⁰ Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai, 200127, China. panqiuhui@scmc.com.cn.
¹¹ Department of Laboratory Medicine, Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center, Sanya, 572000, China. panqiuhui@scmc.com.cn.

^# Contributed equally.

PMID: 37620450
DOI: 10.1038/s41388-023-02808-1

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinogenesis / genetics
Cell Line, Tumor
Cell Proliferation / genetics
Colorectal Neoplasms* / genetics
Gene Expression Regulation, Neoplastic
Humans
Methylation
MicroRNAs* / genetics
MicroRNAs* / metabolism
RNA-Binding Proteins / genetics

Substances

MicroRNAs
RNA-Binding Proteins