Small nucleolar RNA SNORD13H suppresses tumor progression via FBL-dependent 2'-O-methylation in hepatocellular carcinoma

Minglu Zhang^1,2,3,4He Jiambo^1,2,3,4Rao Fu^1,2,3,4Guojian Bao^1,2,3,4Yijun Lu^2,3,4Zechuan Zhang^2,3,4Jiawu Yan^2,3,4Jialu Ding^2,3,4Fei Yang^2,3,4*Beicheng Sun^1,2,3,4*

• ¹Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
• ²The First Affiliated Hospital of Anhui Medical University, Hefei, China
• ³MOE Innovation Center for Basic Research in Tumor Immunotherapy, Hefei, China
• ⁴Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, China

Small nucleolar RNA (snoRNA) mediates RNA modifications, including 2'-O-methylation (Nm) and pseudouridine (Ψ), which has been proved to impact tumor progression. However, the role of snoRNA in the epigenetics of tumors is still poorly understood due to the lack of sufficiently effective experimental methods to identify snoRNA targets. Here, we identified SNORD13H, a C/D box snoRNA, as being downregulated in hepatocellular carcinoma (HCC), and its low expression was associated with HCC development. To elucidate specific roles of SNORD13H in HCC, we employed a comprehensive array of methodologies including flow cytometry, xenograft mouse model, reverse transcription at low dNTP concentration followed by PCR (RTL-P) assay, and surface sensing of translation (SUnSET) assay. In this study, we firstly demonstrated that reduced SNORD13H serve as a biomarker for HCC, facilitating cellular proliferation. SNORD13H mediates 2’-O-methylations of 18S rRNA and RAS mRNA, thereby enhancing translation efficiency and regulating RAS protein levels in HCC. The diminution of SNORD13H activates RAS pathway, contributing to the progression of HCC. Furthermore, our findings indicate that SNORD13H is detectable in plasma, highlighting its potential utility in tumor screening.