circ-CSPP1 promotes proliferation, invasion and migration of ovarian cancer cells by acting as a miR-1236-3p sponge.

Circular RNAs are known to participate in tumorigenesis through a variety of pathways, and as such, have potential to serve as molecular markers in tumor diagnosis and treatment. Here, using quantitative reverse transcription (qRT)-PCR, we showed that circ-CSPP1 is highly expressed in ovarian cancer (OC) tissues. Particularly, we detected circ-CSPP1 expression in three OC cell lines; of which, OVCAR3 and A2780 demonstrated higher levels of circ-CSPP1 expression, and CAOV3 showed lower circ-CSPP1 expression level. Subsequent silencing of circ-CSPP1 in OVCAR3 and A2780 cell lines revealed decreased cell growth, migration and invasion, while overexpression of circ-CSPP1 caused opposite results We also found that miR-1236-3p is a target of circ-CSPP1. Circ-CSPP1 silencing increased the expression of miR-1236-3p, and circ-CSPP1 overexpression decreased miR-1236-3p expression. MiR-1236-3p reportedly plays a tumor-suppressor role in OC by targeting zinc finger E-box binding homeobox 1 (ZEB1). In agreement with this, we showed that silencing circ-CSPP1 significantly decreased ZEB1 expression at both RNA and protein levels, and epithelial-mesenchymal transition (EMT) related markers (E-cadherin and N-cadherin) varied with ZEB1 expression. Circ-CSPP1 silencing also caused decreased expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor A (VEGFA), both of which are related to tumorigenesis. Overexpression of circ-CSPP1 had opposite effects. In addition, we indicated that the tumor-promoting effect was inhibited after we transfected miR-1236-3p into circ-CSPP1 overexpressing OC cells. Altogether, our findings suggest that by acting as a miR-1236-3p sponge, circ-CSPP1 impairs the inhibitory effect of miR-1236-3p on ZEB1, which subsequently promotes EMT and OC development.

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