Dysregulation of lncRNA–miRNA–mRNA Interactome as a Marker of Metastatic Process in Ovarian Cancer

Biomedicines. 2022. Vol. 10. Article 824.

Pronina I., Uroshlev L., Moskovtsev A., Zaichenko D., Filippova E., Fridman M., Burdenny A., Loginov V., Kazubskaya T., Kushlinskii N., Dmitriev A., Braga E., Brovkina O.

Abstract: Ovarian cancer (OC) is one of the most common types of cancer among malignancies of
the female reproductive system. This pathology is asymptomatic until advanced stages and has a
poor prognosis. Our study aimed to search for lncRNA–miRNA–mRNA competing triplets that
promote ovarian tumorigenesis. For this purpose, we analyzed tumor samples from the TCGA
database and verified the results experimentally in a set of 46 paired samples of tumor and matched
histologically unchanged ovarian tissues from OC patients. The list of RNAs selected in silico
for experimental studies included 13 mRNAs, 10 lncRNAs, and 5 miRNAs related to epithelial–
mesenchymal transition and angiogenesis. We evaluated the expression of these RNAs by qRT-PCR
and assessed the correlation between levels of miRNAs, mRNAs, and lncRNAs. Sixteen significant
triplets were revealed, in some of which, e.g., OIP5-AS1–miR-203a–c-MET and OIP5-AS1–miR-203a–
ZEB2, both lncRNA and mRNA had sites for miR-203a direct binding. Transfection of the OVCAR-3
and SKOV-3 cell lines with the miR-203a mimic was used to confirm the novel links of miR-203a
with ZEB2 and c-MET in OC. These connections suggest that the interactomes have the potential for
diagnostics of metastasis at early onset.

Keywords: primary tumor, microRNA, Ovarian cancer, long non-coding RNA, mRNA, differently expressed genes, interactome, triplets