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.

Li QH ，Liu Y ，Chen S ，Zong ZH ，Du YP ，Sheng XJ ，Zhao Y ... -  《-》

Circ-PGAM1 promotes malignant progression of epithelial ovarian cancer through regulation of the miR-542-3p/CDC5L/PEAK1 pathway.

Epithelial ovarian cancer (EOC) is the most common ovarian malignant cancer. Circular RNA is a type of endogenous noncoding RNA and is considered as a novel regulatory molecule in the development and progression of tumors. This study investigated the expression and functions of a circular RNA, circular-phosphoglycerate mutase 1 (circ-PGAM1), in EOC tissues and cells. The expression of circ-PGAM1 and miR-542-3p in EOC was analyzed using quantitative RT-PCR. Immunohistochemistry and western blot were performed to confirm the localization and expression of cell division cycle 5-like (CDC5L) and pseudopodium enriched atypical kinase 1 (PEAK1) in EOC tissues. Cell lines (CAOV3 and OVCAR3) overexpressing or silencingcirc-PGAM1 and miR-542-3p were established to explore the functions of circ-PGAM1 and miR-542-3p in ovarian cancer cells. Furthermore, dual-luciferase reporter assay was performed to study the interactions between circ-PGAM1 and miR-542-3p and between miR-542-3p and CDC5L. CCK-8, transwell, and flow cytometry were used to study the effect of circ-PGAM1 and miR-542-3p on cell biological behaviors including proliferation, migration, invasion, and apoptosis. The interaction between CDC5L and the PEAK1 gene promoter was confirmed using chromatin immunoprecipitation (ChIP). Circ-PGAM1 was upregulated in EOC tissues, whereas linear PGAM1 was not deregulated in EOC tissues. Silencing of circ-PAGM1 inhibited proliferation, migration, and invasion of ovarian cancer cells and promoted cell apoptosis. MiR-542-3p was downregulated in EOC tissues, and miR-542-3p overexpression inhibited malignant progression of ovarian cancer cells. Circ-PGAM1 directly interacted with miR-542-3p, with mutual negative feedback between them. CDC5L was a direct target of miR-542-3p and played an oncogenic role in ovarian cancer cells. Furthermore, the CDC5L protein binds directly to the PEAK1 promoter to promote its transcription. PEAK1 overexpression activated ERK1/2 and JAK2 signaling pathways and promoted malignant biological behaviors of ovarian cancer cells. Circ-PAGM1 silencing combined with miR-542-3p overexpression played the greatest anticancer role in vivo. The circ-PGAM1/miR-542-3p/CDC5L/PEAK1 pathway played an important role in the progression of ovarian cancer and might be a novel therapeutic target for ovarian cancer.

Zhang C ，Li Y ，Zhao W ，Liu G ，Yang Q ... -  《Cancer Medicine》

UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC.

Jin D ，Guo J ，Wu Y ，Du J ，Wang X ，An J ，Hu B ，Kong L ，Di W ，Wang W ... -  《Theranostics》

CircAGFG1 Promotes Ovarian Cancer Progression Through the miR-409-3 p/ZEB1 Axis.

Luo J ，Zhong H ，Guo M ，Xiao P ，Cao R ，Zhao M ，Jing Y ... -  《-》

Circular RNA (hsa_circ_0051240) promotes cell proliferation, migration and invasion in ovarian cancer through miR-637/KLK4 axis.

Zhang M ，Xia B ，Xu Y ，Zhang Y ，Xu J ，Lou G ... -  《-》