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

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

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Abstract Hepatoblastoma (HB) is the most common paediatric liver malignancy.Dysregulation of small nucleolar RNAs (snoRNAs) is a critical inducer of tumour initiation and underwear 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 Stoves Sterling S1000DF 100cm Dual Fuel Range Cooker - Black 444444491 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.