C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2'-O-methylation of PARP1

Abstract Small nucleolar RNAs (snoRNAs), previously thought to function only as housekeeping genes, are dysregulated in many cancers. However, the snoRNAs’ mechanism in tumors remains unclear. We analyzed the expression profiles of snoRNAs in endometrial cancer tissues in data from The Cancer Genome Atlas, and selected SNORD104 as an upregulated snoRNA in endometrial carcinoma. Antisense oligonucleotide (ASO)‑mediated knockdown of SNORD104 in ISHIKAWA cells significantly inhibited cell proliferation, clone formation, and increased apoptosis, while overexpressed SNORD104 from a plasmid promoted endometrial cancer growth in vivo and in vitro. RIP assays showed that SNORD104 binds the 2'-O-methyltransferase, fibrillarin (FBL). Nm-seq showed that SNORD104 upregulated PARP1 (encoding poly (ADP-ribose) polymerase 1) 2'-O-methylation and protein levels. The RIP assay verified that FBL binds to PARP1 mRNA. Correlation analysis showed that SNORD104 expression is positively correlated with PARP1 expression in endometrial cancer tissues. Actinomycin D and cytoplasmic separation assays showed that SNORD104 increased the stability of PARP1 mRNA and promoted its protein nuclear distribution. Silencing FBL or PARP1 in HEC1B cells overexpressing SNORD104 inhibited cell proliferation and clone formation, and promoted cell apoptosis. Thus, SNORD104 enhances PARP1 mRNA stability and protein level by regulating its 2'‑O‑methylation and promotes the growth of endometrial carcinoma.