Abstract
BackgroundCircular RNAs (circRNAs) are gradually reported to be implicated in the development of malignant tumors, including ovarian cancer (OC). This paper intended to explore the function and action mechanism of hsa_circ_0004712 in OC.ResultsIn our results, hsa_circ_0004712 was aberrantly overexpressed in OC tissues and cells. Downregulation of hsa_circ_0004712 impaired OC cell proliferation, colony formation, invasion and migration, and accelerated apoptosis. Hsa_circ_0004712 directly targeted miR-331-3p whose inhibitors reversed the effects of hsa_circ_0004712 downregulation. FZD4 was targeted by miR-331-3p, and hsa_circ_0004712 could positively regulated FZD4 expression by targeting miR-331-3p. The anti-tumor effects of miR-331-3p restoration were reversed by FZD4 overexpression. Downregulation of hsa_circ_0004712 also impaired tumor development in vivo by regulating miR-331-3p and FZD4.ConclusionIn conclusion, hsa_circ_0004712 deficiency repressed OC development by mediating the miR-331-3p/FZD4 pathway, predicting that hsa_circ_0004712 was a promising biomarker for OC diagnosis and therapy.
Highlights
Ovarian cancer (OC) is recognized as the most common and deadly gynecological cancer in women [1, 2]
CircRNA LARP4 was underexpressed in ovarian cancer (OC) tissues and closely linked to the poor prognosis of OC patients [10]
Through dual-luciferase reporter analysis, we found that the transfection of miR-331-3p significantly reduced the luciferase activity of hsa_circ_0004712-wt-transfected cells compared with the control, but did not affect the luciferase activity of the cells transfected with hsa_circ_0004712-mut (Fig. 3B)
Summary
Ovarian cancer (OC) is recognized as the most common and deadly gynecological cancer in women [1, 2]. The primary form of OC is epithelial ovarian cancer (EOC), which accounts for more than 90% of OC cases [3]. Compared with linear precursor mRNA, circRNA is widely distributed and stably expressed because of its covalently closed-loop structure (without 3’ and 5’ ends) [7]. It can be found in exosomes, saliva and plasma [7,8,9]. CircRNAs are considered to be more reliable biomarkers or therapeutic targets in cancers. In OC, numerous circRNAs have been functionally explored. Circular RNAs (circRNAs) are gradually reported to be implicated in the development of malignant tumors, including ovarian cancer (OC). This paper intended to explore the function and action mechanism of hsa_ circ_0004712 in OC
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