23P - Antimetastatic potential of lncRNA group in ovarian carcinoma

Background

Ovarian carcinoma (OC) is characterized by asymptomatic development up to the terminal stages and aggressive metastasis. The study of epigenetic regulation by long non-coding RNAs (lncRNA) that control the level of gene expression is supposed to be promising as they also involved in several aberrant mechanisms during oncogenesis to metastases. We aimed to evaluate the antimetastatic potential of MEG3, MAGI2-AS3, SSTR5-AS1, ZEB1-AS1 lncRNAs through the changes in expression and methylation level of OC.

Methods

RT-qPCR by Bio-Rad with nonparametric Mann–Whitney U test (RStudio) was used.

Results

We revealed statistically significant decrease (p≤0.05, FDR=0.1) of expression for the MEG3, MAGI2-AS3, SSTR5-AS1, ZEB1-AS1 lncRNAs in tumors compared with normal tissues of 30 paired OC samples. At the same time, the methylation level of the genes coding these lncRNAs was statistically significantly higher in tumors (p<0.01, FDR=0.1). Furthermore, the suppressor potential for these lncRNAs was confirmed when analyzing the other stages of OC, in particular, for the lncRNA genes MEG3, SSTR5-AS1, ZEB1-AS1 a statistically significant (p≤0.05, FDR=0.1) increased level of methylation was detected by analyzing the stage, size and grade of the tumor. We also revealed statistically significant decrease in the level of methylation in a set of 19 peritoneal macroscopic metastases (PMM) relative to the paired primary tumors for MEG3, MAGI2-AS3, SSTR5-AS1, ZEB1-AS1 genes (p<0.01, FDR=0.1) and, at the same time, the increase of expression for MEG3 at the trend (p=0.06, FDR=0.1). Thus, the revealed feature may reflect the mechanism of mesenchymal-to-epithelial transition (MET) in “dormant” apparently metastases against primary tumors of OC. Moreover, a strong negative correlation between the levels of methylation and expression for these lncRNAs was revealed: MEG3 (r_s=-0.72, p=0.00002), MAGI2-AS3 (r_s=-0.71, p=0.00002), SSTR5-AS1 (r_s=-0.64, p=0.0002), ZEB1-AS1 (r_s=-0.42, p=0.003).

Conclusions

Based on the results obtained and an additional study on a larger set of samples, it is possible to use these lncRNAs as a novel prognostic marker of metastasis of OC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

FSBSI IGPP.

Funding

The work was supported by the Russian Science Foundation, grant No. 20-15-00368-P.

Disclosure

All authors have declared no conflicts of interest.