SNORA49 negatively regulates self-renewal of liver cancer stem cells and hepatocarcinogenesis via suppressing SOX9 transcription.

ABSTRACT: Cancer stem cells (CSCs) play a critical role in tumor initiation, progression, and recurrence. How liver CSCs initiate their self-renewal remains elusive. Here we identify a conserved small nucleolar RNA (snoRNA), SNORA49, which is lowly expressed in liver CSCs, as a negative regulator of CSC self-renewal. SNORA49 knockout enhances the self-renewal capacity of liver CSCs and accelerates hepatocellular carcinoma (HCC) tumorigenesis, whereas overexpression of SNORA49 suppresses tumor formation. Mechanistically, in non-CSCs, SNORA49 is specifically localized in the nucleoplasm to associate with HNRNPU, blocking its interaction with ZC3H18, resulting in inhibition of SOX9 transcription. In liver CSCs, lowly expressed SNORA49 releases HNRNPU to engage with ZC3H18 and enrich on the promoter of

SUBMITTER: Yi Z 

PROVIDER: S-EPMC12824223 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature