Objective: The dysregulation of ribosome biogenesis is associated with the progression of numerous tumors, including hepatocellular carcinoma (HCC). Small nucleolar RNAs (snoRNAs) regulate ribosome biogenesis by guiding the modification of ribosomal RNAs (rRNAs). However, the underlying mechanism of this process in HCC remains elusive. Methods: RNA immunoprecipitation and sequencing were used to analyze RNAs targeted by ribosome proteins. The biological functions of SNORA23 were examined in HCC cells and a xenograft mouse model. To elucidate the underlying mechanisms, the 2′-O-ribose methylation level of rRNAs was evaluated by qPCR, and the key proteins in the PI3K/Akt/mTOR pathway were detected using Western blot. Results: Twelve snoRNAs were found to co-exist in 4 cancer cell lines using RPS6 pull-down assays. SNORA23 was downregulated in HCC and correlated with the poor prognoses of HCC patients. SNORA23 inhibited the proliferation, migration, and invasion of HCC cells both in vitro and in vivo. We also found that SNORA23 regulated ribosome biogenesis by impairing 2′-O-ribose methylation of cytidine4506 of 28S rRNA. Furthermore, SNORA23, which is regulated by the PI3K/Akt/mTOR signaling pathway, significantly inhibited the phosphorylation of 4E binding protein 1. SNORA23 and rapamycin blocked the PI3K/AKT/mTOR signaling pathway and impaired HCC growth in vivo. Conclusions: SNORA23 exhibited antitumor effects in HCC and together with rapamycin, provided a promising therapeutic strategy for HCC treatment.

Zhiyong Liu;Yanan Pang;Yin Jia;Qin Qin;Rui Wang;Wei Li;Jie Jing;Haidong Liu;Shanrong Liu

Department of Laboratory Diagnostics,Changhai Hospital,Second Military Medical University,Shanghai 200433,China;Department of Gastroenterology and Hepatology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Gastroenterology,Changhai Hospital,Second Military Medical University,Shanghai 200433,China;Shanghai Institute of Pancreatic Diseases,Shanghai 200433,China;Department of Chemistry and State Key Laboratory of Molecular Engineering of Polymers,Fudan University,Shanghai 200433 China;Department of General Surgery,Changzheng Hospital,Second Military Medical University,Shanghai 200433,China;Shanghai Fourth People's Hospital,Tongji University School of Medicine,Shanghai 200081,China

癌症生物学与医学（英文版）

[1]Zhiyong Liu;Yanan Pang;Yin Jia;Qin Qin;Rui Wang;Wei Li;Jie Jing;Haidong Liu;Shanrong Liu-.SNORA23 inhibits HCC tumorigenesis by impairing the 2?-O-ribose methylation level of 28S rRNA)[J].癌症生物学与医学（英文版）,2022(01):104-119

SNORA23,cytidine4506

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