Introduction: Understanding highly invasive ovarian cancer development is crucial for early detection. While in many cases, histological differences between highly invasive tumours like high-grade serous carcinomas (HGSC) and benign serous borderline tumors (SBT) are clear, the molecular factors driving their distinct invasive potential remain unclear. Revealing the invasive potential of these different types of ovarian tumours may reveal markers and therapeutic targets.

Methods & Results: The H/ACA box snoRNA, SNORA81, is overexpressed in high-grade ovarian cancer and can differentiate between normal fallopian tubes, SBT and HGSC tissues. SNORA81 deletion in high-grade ovarian cancer cell lines inhibits proliferation, migration, and cell invasiveness. Increased SNORA81 expression leads to increased ribosomal RNA (rRNA) pseudouridylation, suggesting its role in promoting tumour aggressiveness through ribosome function modulation. To study its capacity to promote tumour development, SNORA81 was overexpressed in the immortalized normal ovarian cell line INOF. Interestingly, the overexpression of this single snoRNA markedly increased cell migration potential. Still, while the knockdown of SNORA81 does not modify the overall translation pattern, it alters translation of key mRNAs. Amongst are genes, known as tumour suppressors and inhibitors of the Wnt pathway. Thus, we hypothesize that SNORA81 modifies ribosome preference in HGSC to repress the translation of genes that act as inhibitors of the Wnt pathway, ultimately increasing cancer cell invasiveness.

Conclusion: We identified a new regulatory layer in the Wnt pathway affecting tumour invasive potential. In this new model of regulation, increasing the modification of a single residue in rRNA represses the translation of tumour suppressors involved in the Wnt pathway. This finding highlights how ribosomes may influence cancer biology and adds translation as an important regulatory layer of cancer-associated genes.