Tumor-associated miR-124 and miR-137 in post-transcriptional regulation of ovarian cancer

¹ Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
² Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia
³ N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia

Academic Editor: Masaharu Seno

Published: 05 June 2026 by MDPI in The 5th International Electronic Conference on Cancers session Tumor Heterogeneity

Abstract:

Introduction: Ovarian cancer (OvCa) exhibits high mortality due to asymptomatic progression and early metastasis. Long noncoding RNAs (lncRNAs) and miRNAs are vital regulators and potential therapeutic targets. We investigated the ceRNA (lncRNA/miRNA/mRNA) mechanisms involving miR-124 and miR-137 in OvCa.

Methods: Bioinformatics screening of targets for miR-124 and miR-137 used GSE211669 and GSE119055 datasets (NCBI GEO). SKOV3 and OVCAR3 cells were transfected with miR-124-3p and miR-137-3p mimics, followed by Affymetrix HTA 2.0 microarray analysis. Expression of lncRNAs and mRNAs was validated via RT-qPCR in 56 paired (T/N) clinical OvCa samples using TaqMan assays.

Results: Bioinformatics identified lncRNAs GAS5, MEG3, and ZNF667-AS1, and 15 mRNA targets (r < -0.6, 7-8mer sites). Experimental validation in cell cultures and clinical samples confirmed the following regulatory axes:

GAS5 / miR-124-3p, -5p / ANAPC1, HLTF, IL15, PARP14, TRAF3, ZEB1.
GAS5, MEG3, ZNF667-AS1 / miR-137-3p / ANAPC1, HLTF, RNF169, TRAF3, VIM, ZEB1.
Strong positive correlations between lncRNAs and target mRNAs (p < 0.05) support the ceRNA sponging mechanism.

Conclusions: The observed findings may reflect intratumoral heterogeneity in ovarian cancer. The identified ceRNA axes exhibit variability in both expression levels and the strength of correlation patterns across clinical samples, which may be attributed to differences in molecular subtypes, cellular composition, and the extent of the epithelial–mesenchymal transition. Regulation of key genes, including ZEB1, VIM, and TRAF3, through lncRNA/miRNA/mRNA networks likely contributes to the emergence of functionally distinct tumor cell subpopulations, including those with increased metastatic and immunosuppressive potential. Collectively, these findings suggest that the identified ceRNA networks may act not only as regulatory frameworks but also as indicators of tumor molecular heterogeneity, with potential implications for patient stratification and the development of personalized therapeutic strategies.

Keywords: Ovarian cancer, Long noncoding RNAs, miRNAs, miR-124 and miR-137