2. Academic Validation
  3. SNORA14A inhibits hepatoblastoma cell proliferation by regulating SDHB-mediated succinate metabolism

SNORA14A inhibits hepatoblastoma cell proliferation by regulating SDHB-mediated succinate metabolism

  • Cell Death Discov. 2023 Jan 30;9(1):36. doi: 10.1038/s41420-023-01325-0.
Jiabei Zhu # 1 2,  Siwei Mao # 1 2,  Ni Zhen 1,  Guoqing Zhu 1,  Zhixuan Bian 1,  Yi Xie 1,  Xiaochen Tang 1,  Miao Ding 1,  Han Wu 1,  Ji Ma 1,  Yizhun Zhu 3,  Fenyong Sun 4,  Qiuhui Pan 5 6 7
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • 2 Shanghai Key Laboratory of Clinical Molecular Diagnostics for Paediatrics, Shanghai, 200127, China.
  • 3 State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, 999078, China.
  • 4 Department of Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China. sunfenyong@263.net.
  • 5 Department of Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. panqiuhui_med@163.com.
  • 6 Shanghai Key Laboratory of Clinical Molecular Diagnostics for Paediatrics, Shanghai, 200127, China. panqiuhui_med@163.com.
  • 7 Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center, Sanya, 572000, China. panqiuhui_med@163.com.
  • # Contributed equally.
PMID: 36717552 DOI: 10.1038/s41420-023-01325-0
Abstract

Hepatoblastoma (HB) is the most common paediatric liver malignancy. Dysregulation of small nucleolar RNAs (snoRNAs) is a critical inducer of tumour initiation and progression. However, the association between snoRNAs and HB remains unknown. Here, we conducted snoRNA expression profiling in HB by snoRNA sequencing and identified a decreased level of SNORA14A, a box H/ACA snoRNA, in HB tissues. Low expression of SNORA14A was correlated with PRETEXT stage and metastasis in patients. Functionally, overexpression of SNORA14A suppressed HB cell proliferation and triggered cell Apoptosis and G2/M phase arrest. Mechanistically, SNORA14A overexpression promoted the processing and maturation of the 18 S ribosomal RNA (rRNA) precursor to increase succinate dehydrogenase subunit B (SDHB) protein levels. In accordance with SNORA14A downregulation, SDHB protein expression was significantly reduced in HB tissues and cells, accompanied by abnormal accumulation of succinate. Overexpression of SDHB showed antiproliferative and proapoptotic effects and the capacity to induce G2/M phase arrest, while succinate dose-dependently stimulated HB cell growth. Furthermore, the inhibition of SNORA14A in HB malignant phenotypes was mediated by SDHB upregulation-induced reduction of cellular succinate levels. Therefore, the SNORA14A/18 S rRNA/SDHB axis suppresses HB progression by preventing cellular accumulation of the oncometabolite succinate and provides promising prognostic biomarkers and novel therapeutic targets for HB.

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