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Noncoding RNA Res. 2025 Jul 23;15:74-84. doi: 10.1016/j.ncrna.2025.07.005. eCollection 2025 Dec.
ABSTRACT
Ovarian carcinoma (OC) exhibits a 5-year survival rate of below 40 %, mainly due to late-stage diagnosis and recurrence associated to resistance to chemotherapy. Long noncoding RNAs (lncRNAs) are involved in numerous cellular processes of critical physiological relevance and dysregulation of their expression has been implicated in various pathologies, including cancer. However, the functions and mechanisms of the majority of them remains largely uncharacterized. To investigate their potential roles in treatment response, we performed RNA sequencing (RNA-Seq) on 47 High Grade Serous Ovarian Carcinoma (HGSOC) samples, including 28 from patients who achieved a complete response to first-line therapy and 19 from those with partial response or stable disease. Among the differentially expressed transcripts, we identified MYO16-AS1, a poorly characterized lncRNA, whose overexpression correlated with decreased overall survival (OS) in OC. Functional assays revealed that MYO16-AS1 downregulation significantly impairs proliferation, migration and invasion in SKOV3 ovarian cancer cell line. Integrative transcriptomic and proteomic analyses further demonstrated that MYO16-AS1 regulates a network of genes associated with these oncogenic processes. Notably, we identified MICAL2 as a key downstream effector, whose downregulation induces similar consequences observed upon MYO16-AS1 downregulation, suggesting that MICAL2 is a major mediator of the functional effect of MYO16-AS1 in OC. Strikingly, MICAL2 inhibition markedly reduced proliferation accross several OC patient-derived tumor organoid models, regardless of their response to chemotherapy, thereby underscoring MICAL2 as a promising therapeutic target in OC.
PMID:40822859 | PMC:PMC12351189 | DOI:10.1016/j.ncrna.2025.07.005