ИСТИНА

Ovarian cancer (OC) develops asymptomatically and worldwide is accompanied by the highest mortality among oncological diseases of the female reproductive system. The discovery of long noncoding RNAs (lncRNAs) opens up new opportunities in the study of cancer pathogenesis, including the mechanism of gene regulation according to the the ceRNA model. The aim of this work is to identify new lncRNAs potentially involved in the regulation of tumor-associated proteins mediated by miRNAs, namely, 12 miRNAs, which, according to our data, are involved in metastasis of the OC (Loginov et al., 2018). Bioinformatic screening of lncRNAs was performed based on the TCGA transcriptome database (package GENIE3) using modified random forest method. A total of 345 experiments were retrieved containing information on RNAs in OC samples. First, lncRNAs were selected, potentially binding to 10 metastasis-associated miRNAs (miR-124, -125b, -129, -148a, -203, -375 and etc.; rs = 0–1, P < 0.002). Second, lncRNA/miRNA/mRNA triplets were selected, including 10 target miRNAs, using all significant pairs “lncRNA-miRNA”and “miRNA-mRNA”(rs = 0–1, P < 0.002). Expression level of 10 target miRNAs and selected 15 lncRNAs and 25 protein mRNAs was studied by qRT-PCR using a common set of 40 matched (tumor/normal) samples of OC. Negative correlations were revealed between the levels of RNA of different types (rs = [- 0.33] - [-0.63], P = 0.00–0.05), indicating potential interactions within 7 pairs of lncRNA/miRNA, e.g. MALAT1/ miR-191, MAFG-DT/miR-148a, OIP-AS1/miR-203, and 11 miRNA/mRNA pairs as miR-148a/BCL2, miR-203/CDK4, miR- 375/WNT4. The triple interactions, e.g. MALAT1/miR-203/ CDK4, MAFG-DT/miR-148a/BCL2 were also revealed. Of interest, 90 positive correlations between lncRNAs and protein mRNAs were detected. The most significant results would be verified in functional studies using transfection of OC cell lines. This work was supported by the Russian Science Foundation, grant no. 20-15-00368