Theranostics 2020; 10(20):9348-9363. doi:10.7150/thno.47677

Research Paper

The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1

Cuicui Li1, Long Wu2, Pengpeng Liu2, Kun Li2, Zhonglin Zhang2, Yueming He2, Quanyan Liu2, Ping Jiang2, Zhiyong Yang2, Zhisu Liu2, Yufeng Yuan2✉, Lei Chang2✉

1. Department of Integrated Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China.
2. Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China.

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Citation:
Li C, Wu L, Liu P, Li K, Zhang Z, He Y, Liu Q, Jiang P, Yang Z, Liu Z, Yuan Y, Chang L. The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1. Theranostics 2020; 10(20):9348-9363. doi:10.7150/thno.47677. Available from https://www.thno.org/v10p9348.htm

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Abstract

Rationale: Understanding the roles of small nucleolar RNAs (snoRNAs) in hepatocarcinogenesis will provide new avenues to identify diagnostic and therapeutic targets for hepatocellular carcinoma (HCC). Our previous research confirmed the tumor-suppressive effect of Up-frameshift 1 (Upf1) in HCC. Herein, we examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells.

Methods: We examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells using RNA-sequencing analysis and then investigated the expression and significance of SNORD52 in HCC tissue and different cell lines. The protumorigenic effects of SNORD52 on HCC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function assays. RNA pull-down assays and mass spectrometry were used to identify the RNA-binding protein that binds to SNORD52.

Results: Many snoRNAs were identified; one of which, the human C/D box small nucleolar RNA SNORD52, was upregulated in HCC tissues and negatively correlated with Upf1 expression, and patients with higher SNORD52 expression had a poor clinical prognosis. SNORD52 promoted HCC tumorigenesis both in vitro and in vivo. Mechanistically, KEGG analysis showed that SNORD52 upregulated a series of cell cycle genes in HCC cells. We further confirmed that SNORD52 upregulated CDK1 by enhancing the stability of CDK1 proteins and that the function of SNORD52 depends on the presence of CDK1.

Conclusion: Overall, the present study indicates that SNORD52 could be a potential biomarker for HCC. Targeting the Upf1/SNORD52/CDK1 pathway might have therapeutic potential for HCC.

Keywords: Hepatocellular carcinoma, Upf1, SNORD52, Hepatocarcinogenesis