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SNORD88C guided 2′-O-methylation of 28S rRNA regulates SCD1 translation to inhibit autophagy and promote growth and metastasis in non-small cell lung cancer

Abstract

Small nucleolar RNAs (snoRNAs) have been shown to play critical regulatory roles in cancer development. SNORD88C, which located at the intronic region of C19orf48 in chromosome 19q.33 with a 97-nt length was screened through database and snoRNA-sequencing. We firstly verified this snoRNA was up-regulated in tissue and plasma and served as a non-invasive diagnostic biomarker; then confirmed that SNORD88C promoted proliferation and metastasis of NSCLC in vitro and in vivo. Mechanistically, SNORD88C promoted 2′-O-methylation modification at the C3680 site on 28S rRNA and in turn enhanced downstream SCD1 translation, a central lipogenic enzyme for the synthesis of MUFA that can inhibit autophagy by regulating lipid peroxidation and mTOR, providing the novel insight into the regulation of SNORD88C in NSCLC.

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Fig. 1: SNORD88C is up-regulated in NSCLC and serves as a non-invasive diagnostic biomarker.
Fig. 2: SNORD88C promotes proliferation of NSCLC in vitro and in vivo.
Fig. 3: SNORD88C promotes NSCLC migration and invasion in vitro and in vivo.
Fig. 4: SNORD88C-attenuated autophagy is required for its promotion of migration and invasion.
Fig. 5: SNORD88C inhibits autophagy via upregulating SCD1 protein expression.
Fig. 6: SNORD88C regulates the translation activity of SCD1 though guiding 2′-O-me of 28S rRNA.

Data availability

All relevant data are available from the corresponding author upon reasonable request. In addtion, raw data from snoRNA sequencing and protein mass spectrometry were uploaded to the GAS-Human (HRA003325) and OMIX (OMIX002173) databases of CNCB-NGDC (China National Center for Bioinformation-National Genomics Data Center).

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Acknowledgements

We thank Hualei Yu for technical assistance of polysome profiling experiment and Xiujie Cui for the animal care.

Funding

This work was supported by the National Natural Science Foundation of China (81972014), the Shandong Provincial Natural Science Foundation (ZR2019MH004 and ZR2019LZL016) and Shandong Provincial Key Research and Development Program (Major Science & Technology Innovation Project) (2021SFGC0501).

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SX and SX designed and conceived the research content. Wang Kangyu performed sample collection, experiments, data analysis and wrote the manuscript. SX guided the experiments and reviewed the manuscript. WS carried out the Western blot assay. ZY extracted RNA of FFPE samples. SX, XL, and SX contributed reagents materials, instruments, analytic tools, and grant support. The author(s) read and approved the final manuscript.

Corresponding authors

Correspondence to Xingguo Song or Xianrang Song.

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The studies involving human participants (201806004) and animals (201911025) were reviewed and approved by Ethics Committee of Shandong Cancer Hospital and Institute.

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Wang, K., Wang, S., Zhang, Y. et al. SNORD88C guided 2′-O-methylation of 28S rRNA regulates SCD1 translation to inhibit autophagy and promote growth and metastasis in non-small cell lung cancer. Cell Death Differ (2022). https://doi.org/10.1038/s41418-022-01087-9

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