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Updated: Mar 23, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
miR-509-3p is clinically significant and strongly attenuates cellular migration and multi-cellular spheroids in
Yinghong Pan1, Gordon Robertson2, Lykke Pedersen3
1Department of Biochemistry and Biology, University of Houston, Houston, TX, USA.
Abstract:
Ovarian cancer presents as an aggressive, advanced stage cancer with widespread metastases that depend primarily on multicellular spheroids in the peritoneal fluid. To identify new druggable pathways related to metastatic progression and spheroid formation, we integrated microRNA and mRNA sequencing data from 293 tumors from The Cancer Genome Atlas (TCGA) ovarian cancer cohort. We identified miR-509-3p as a clinically significant microRNA that is more abundant in patients with favorable survival in both the TCGA cohort (P = 2.3E-3), and, by in situ hybridization (ISH), in an independent cohort of 157 tumors (P < 1.0E-3). We found that miR-509-3p attenuated migration and disrupted multi-cellular spheroids in HEYA8, OVCAR8, SKOV3, OVCAR3, OVCAR4 and OVCAR5 cell lines. Consistent with disrupted spheroid formation, in TCGA data miR-509-3p's most strongly anti-correlated predicted targets were enriched in components of the extracellular matrix (ECM). We validated the Hippo pathway effector YAP1 as a direct miR-509-3p target. We showed that siRNA to YAP1 replicated 90% of miR-509-3p-mediated migration attenuation in OVCAR8, which contained high levels of YAP1 protein, but not in the other cell lines, in which levels of this protein were moderate to low. Our data suggest that the miR-509-3p/YAP1 axis may be a new druggable target in cancers with high YAP1, and we propose that therapeutically targeting the miR-509-3p/YAP1/ECM axis may disrupt early steps in multi-cellular spheroid formation, and so inhibit metastasis in epithelial ovarian cancer and potentially in other cancers.
Insights
MicroRNA-509-3p is linked to better ovarian cancer survival and inhibits metastasis by targeting YAP1 and disrupting extracellular matrix interactions, suggesting a new therapeutic pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Ovarian cancer is aggressive, characterized by widespread metastasis driven by multicellular spheroids in peritoneal fluid.
- Identifying novel druggable targets for metastatic progression and spheroid formation is crucial for improving patient outcomes.
Purpose of the Study:
- To identify microRNAs (miRNAs) and their associated pathways involved in ovarian cancer metastasis and spheroid formation.
- To investigate the role of miR-509-3p and its potential targets in regulating cancer cell behavior and extracellular matrix interactions.
Main Methods:
- Integrated miRNA and mRNA sequencing data from The Cancer Genome Atlas (TCGA) ovarian cancer cohort (n=293).
- Validated miR-509-3p significance using in situ hybridization (ISH) on an independent cohort (n=157).
- Assessed miR-509-3p effects on cell migration and spheroid formation in multiple ovarian cancer cell lines.
- Identified and validated direct targets of miR-509-3p, including the Hippo pathway effector YAP1.
Main Results:
- miR-509-3p was identified as a clinically significant miRNA, with higher abundance correlating with favorable survival in both TCGA and independent cohorts.
- miR-509-3p significantly attenuated cancer cell migration and disrupted multicellular spheroid formation in vitro.
- TCGA data revealed that predicted miR-509-3p targets were enriched in extracellular matrix (ECM) components.
- YAP1 was validated as a direct miR-509-3p target, and its knockdown mimicked miR-509-3p's effect on migration in YAP1-high cells.
Conclusions:
- The miR-509-3p/YAP1 axis represents a novel druggable target, particularly in ovarian cancers with high YAP1 expression.
- Targeting the miR-509-3p/YAP1/ECM axis may inhibit early spheroid formation and reduce metastasis in epithelial ovarian cancer.
- This axis holds potential for therapeutic intervention in other cancers exhibiting similar metastatic mechanisms.
