Abstract
BackgroundCircular RNA (circRNA) has been shown to be involved in the regulation of human disease progression, including ovarian cancer (OC). Circ_0078607 was found to participate in OC progression. But its function and mechanism in OC deserve further exploration.MethodsThe expression levels of circ_0078607, salt-inducible kinase 1 (SIK1) and microRNA (miR)-32-5p were examined by qRT-PCR. And the protein expression levels of SIK1, metastasis marker and apoptosis marker were determined using western blot analysis. EDU staining, colony formation assay, transwell assay and flow cytometry were used to detect the proliferation, migration, invasion and apoptosis of cells. Moreover, dual-luciferase reporter assay was employed to verify the interaction between miR-32-5p and circ_0078607 or SIK1. Xenograft models were constructed to perform in vivo experiments.ResultsCirc_0078607 and SIK1 were downregulated in OC tissues and cells. Overexpressed circ_0078607 and SIK1 could inhibit OC cell proliferation, migration, invasion, and promote apoptosis. MiR-32-5p could be sponged by circ_0078607, and its overexpression could reverse the suppressive effect of circ_0078607 on OC progression. Furthermore, SIK1 was a target of miR-32-5p, and circ_0078607 could regulate SIK1 by sponging miR-32-5p. The inhibitory effect of circ_0078607 on OC progression also could be reversed by SIK1 silencing. In vivo experiments showed that circ_0078607 reduced OC tumorigenesis by regulating the miR-32-5p/SIK1 axis.ConclusionCirc_0078607 could serve as a sponge of miR-32-5p to regulate SIK1 expression, thereby inhibiting OC progression.
Highlights
Ovarian cancer (OC) is a malignant tumor that occurs in the ovary and is the biggest disease that seriously threatens women’s health [9, 20]
Circ_0078607 and salt-inducible kinase 1 (SIK1) were lowly expressed and positively correlated in ovarian cancer (OC) tissues In OC tumor tissues, we discovered that circ_0078607 was downregulated compared with that in adjacent normal tissues (Fig. 1A)
The correlation analysis results showed that there was a significant positive correlation between the expression of circ_0078607 and SIK1 in OC tumor tissues (Fig. 1D). These results suggested that circ_0078607 and SIK1 might play the important roles in the progression of OC
Summary
Ovarian cancer (OC) is a malignant tumor that occurs in the ovary and is the biggest disease that seriously threatens women’s health [9, 20]. Studies have found that circRNA is widely and diversely present in a variety of biological cells and has the regulating effect on gene expression [1, 2]. The researchers have found that the expression of circRNA is closely related to the progression of many human diseases, including OC [19, 22]. Circular RNA (circRNA) has been shown to be involved in the regulation of human disease progression, including ovarian cancer (OC). Overexpressed circ_0078607 and SIK1 could inhibit OC cell proliferation, migration, invasion, and promote apoptosis. In vivo experiments showed that circ_0078607 reduced OC tumorigenesis by regulating the miR-32-5p/SIK1 axis. Conclusion: Circ_0078607 could serve as a sponge of miR-32-5p to regulate SIK1 expression, thereby inhibiting OC progression
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