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

Oncogene volume 42, pages 3035–3046 (2023)Cite this article

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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.

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Fig. 1: snoRNA-seq reveals the snoRNA expression profile of CRC tissues.
Fig. 2: Identification of SNORD11B as an upregulated snoRNA in CRC.
Fig. 3: SNORD11B knockdown inhibits CRC malignancy in vitro and in vivo.
Fig. 4: SNORD11B mediates Nm modification on G509 site of 18S rRNA.
Fig. 5: SNORD11B negatively regulates let-7-family miRNA expression.
Fig. 6: SNORD11B mediated Nm modification on G225 site of MIRLET7A1HG.
Fig. 7: The oncogenic role of SNORD11B in CRC depends on let-7a-5p.
Fig. 8: Proposed model.

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Data availability

All data generated in this study are present in the paper and/or the Supplementary Files. The snoRNA-seq data have been deposited in the China National Centre for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (GSA: HRA003909) and are publicly accessible at https://ngdc.cncb.ac.cn/gsa.

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Acknowledgements

This work was sponsored by the National Natural Science Foundation of China (82172357, 82293662), Key project of Shanghai “Science and Technology Innovation Action Plan” (22JC1402300), Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR2061B), the Joint Project of Pudong New Area Municipal Health Commission of Shanghai (PW2019D-10), and Shanghai Sailing Program (20YF1428600).

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Author notes

  1. These authors contributed equally: Zhixuan Bian, Chang Xu, Yi Xie.

Authors and Affiliations

  1. Department of Laboratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

    Zhixuan Bian, Yi Xie, Siwei Mao, Jiabei Zhu, Ji Ma & Qiuhui Pan

  2. College of Health Science and Technology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China

    Zhixuan Bian, Yi Xie, Siwei Mao, Jiabei Zhu, Ji Ma & Qiuhui Pan

  3. Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai, 200127, China

    Zhixuan Bian, Yi Xie, Siwei Mao, Jiabei Zhu, Ji Ma & Qiuhui Pan

  4. Department of Laboratory Medicine, Sanya Women and Children’s Hospital Managed by Shanghai Children’s Medical Center, Sanya, 572000, China

    Zhixuan Bian & Qiuhui Pan

  5. Department of Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, 200072, China

    Chang Xu, Xiaoying Wang, Yan Chen, Qi Wu, Nan Huang & Fenyong Sun

  6. Department of Central Laboratory, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, 200072, China

    Yue Zhang

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Contributions

Conceptualization, QP and FS; Methodology, ZB, CX and YX; Clinical samples and information collection, YX, XW, YC, QW and NH. Statistical Analysis, ZB, SM, YX and JZ. Animal experiment, ZB, CX and YZ. Investigation, ZB, CX and JZ. Writing-Original Draft, ZB; Supervision, QP and FS. All authors reviewed the manuscript.

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Correspondence to Fenyong Sun or Qiuhui Pan.

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Bian, Z., Xu, C., Xie, Y. et al. SNORD11B-mediated 2′-O-methylation of primary let-7a in colorectal carcinogenesis. Oncogene 42, 3035–3046 (2023). https://doi.org/10.1038/s41388-023-02808-1

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