SNORD11B-mediated 2′-O-methylation of primary let-7a in colorectal carcinogenesis

Abstract Evidence indicates that small nucleolar RNAs (snoRNAs) participate in tumorigenesis and development and could be promising biomarkers for colorectal cancer (CRC). Here, we examine the profile of snoRNAs in CRC and find that expression of SNORD11B is increased in CRC tumor tissues and cell lines, with a significant positive correlation between SNORD11B expression and that of its host gene NOP58. SNORD11B promotes CRC cell proliferation and invasion and inhibits apoptosis. Mechanistically, SNORD11B promotes the processing and maturation of 18S ribosomal RNA (rRNA) by mediating 2'-O-methylated (Nm) modification on the G509 site of 18S rRNA. Intriguingly, SNORD11B mediates Nm modification on the G225 site of MIRLET7A1HG (pri-let-7a) with canonical motif, resulting in degradation of pri-let-7a, inhibition of DGCR8 binding, reduction in mature tumor suppressor gene let-7a-5p expression, and upregulation of downstream oncogene translation. SNORD11B performs better than CEA and CA199 in diagnosing CRC. High expression of SNORD11B is significantly correlated with more advanced TNM stage and lymph node metastasis, which indicate poor prognosis.