Introduction: Small nucleolar RNAs (snoRNAs) are non-coding RNAs involved in ribosomal RNA modifications. Recent snoRNA-sensitive high-throughput sequencing highlighted specific H/ACA snoRNAs, including SNORA81, upregulated in high-grade serous ovarian cancer (HGSC). SNORA81 knockdown (KD) reduces cell invasiveness, while its overexpression (OVE) in non-cancerous ovarian cells promotes migration. This study aims to decipher pathways through which SNORA81 influences tumor invasiveness, establishing a correlation between SNORA81 and ovarian cancer progression.

Methods: SNORA81’s impact on gene expression was assessed by knocking it down in the OVCAR-3 cell line (representing HGSC) and overexpressing it in the INOF cell line (immortalized normal ovarian cells). Using RNA-seq, we identified genes correlating with SNORA81 levels in HGSC, serous borderline tumor (SBT), and normal fallopian tube tissues. We assessed these genes’ involvement in SNORA81-associated phenotypes through KD or OVE experiments.

Results: Comparative sequencing analysis identified three genes that are modulated by SNORA81 in both tissues and cell lines. SOCS1, a known ovarian cancer suppressor, is downregulated in HGSC compared to SBT and upregulated upon SNORA81 KD in OVCAR-3 cells. Conversely, IRAK1 (associated with breast cancer metastasis and ovarian cancer) and SPC24 (a component of the NDC80 kinetochore complex influencing cancer progression via the PI3K/AKT/mTOR pathway), are upregulated in HGSC but downregulated following SNORA81 KD.

Conclusion: This study elucidates the relationship between ovarian cancer invasiveness and H/ACA snoRNAs, particularly SNORA81, orchestrating critical oncogenes and tumor suppressors. SNORA81 modulation may alter key cancer pathways, influencing ovarian cancer invasiveness, proposing SNORA81 as a potential therapeutic target for managing ovarian cancer aggressiveness.