Expression of circERBB2 in ovarian cancer and its mechanism

Objective To investigate the expression and mechanism of circERBB2 in ovarian cancer.

Methods The GEO database was used to screen differentially expressed circular RNAs (circRNAs) in ovarian cancer, and to search for target genes related to circRNAs. A Venn plot was drawn to obtain the cross genes between differentially expressed genes in the GSE79572 dataset and the small RNA-187-3p (miR-187-3p) target genes predicted by Targetscan 7.1. Ovarian cancer tissue and adjacent normal tissue from 20 ovarian cancer patients were collected. Human normal ovarian cell line HOSEpiC and human ovarian cancer cell lines OVCAR-3, SKOV-3, 3AO, OV90 were cultured. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the levels of circERBB2, miR-187-3p, and BCL6. The interactions among circERBB2, miR-187-3p and BCL6 were verified by double Luciferase reporter gene experiment and RNA pull-down experiment. The effects of circERBB2, miR-187-3p, and BCL6 on invasion, migration, proliferation, and cell cycle of ovarian cancer cells were explored.

Results The database analysis showed that the differentially expressed circRNA in ovarian cancer was circERBB2, and the miRNA targeted by circERBB2 was miR-187-3p. After drawing a Venn plot for intersection, seven cross genes such as BCL6 were obtained. There were potential binding sites between circERBB2 and miR-187-3p, as well as miR-187-3p and BCL6. The levels of circERBB2 and BCL6 in ovarian cancer tissue were higher than those in adjacent tissues, while the level of miR-187-3p was lower than that in adjacent tissues (P < 0.05). The expression levels of circERBB2 in ovarian cancer cell lines OVCAR-3, SKOV-3, 3AO, and OV90 were higher than those in normal ovarian cell lines HOSEpiC (P < 0.05). The double luciferase reporter gene experiment and RNA pull-down experiment confirmed that circERBB2, miR-187-3p and BCL6 had interaction relationships. Multiple cell experiments have shown that silencing circERBB2 expression can inhibit the proliferation and migration of ovarian cancer cells, and this inhibitory effect can be reversed by overexpression of miR-187-3p. Inhibition of miR-187-3p can effectively promote the proliferation and migration of ovarian cancer cells, which can be reversed after inhibiting the expression of BCL6.

Conclusion CircERBB2 can promote the expression of the oncogene BCL6 through targeted adsorption of miR-187-3p, thereby regulating the occurrence of ovarian cancer.