Abstract
BackgroundOvarian cancer is an aggressive tumor in women with high mortality. Paclitaxel (PTX) can be used for the chemotherapy of ovarian cancer. Here, the roles of circular_0061140 (circ_0061140) in PTX sensitivity and malignant progression of ovarian cancer are unveiled.MethodsThe expressions of circ_0061140, microRNA-136 (miR-136) and chromobox 2 (CBX2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot. The half maximal inhibitory concentration (IC50) of PTX was determined by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was investigated by cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by transwell assay. The binding relationship between miR-136 and circ_0061140 or CBX2 was predicted by interactome or starbase online database, and identified by dual-luciferase reporter assay. The effects of circ_0061140 on tumor formation and PTX sensitivity in vivo were disclosed by tumor formation assay.ResultsCirc_0061140 and CBX2 expressions were upregulated, while miR-136 expression was downregulated in PTX-resistant tissues and cells compared with control groups. Circ_0061140 knockdown repressed cell proliferation, migration and invasion, and promoted cell apoptosis and PTX sensitivity; however, these effects were restrained by miR-136 RNAi. Additionally, circ_0061140 was a sponge of miR-136, and miR-136 bound to CBX2. Furthermore, circ_0061140 knockdown inhibited tumor formation and improved PTX sensitivity in vivo.ConclusionsCirc_0061140 silencing repressed the progression and PTX resistance of ovarian cancer by downregulating CBX2 expression via sponging miR-136, which provided novel insight into studying the therapy of ovarian cancer with PTX.
Highlights
Ovarian cancer is an aggressive tumor in women with high mortality
Circ_0061140 expression was significantly upregulated in SKOV3/PTX and HeyA8/PTX cells compared with SKOV3 and HeyA8 cells (Fig. 1D and E)
The mRNA and protein expressions of chromobox 2 (CBX2) were apparently decreased by PTX, whereas these influences were promoted by circ_0061140 silencing (Fig. 7E and F). These results demonstrated that circ_0061140 could mediated PTX sensitivity and tumor formation by modulating miR-136 and CBX2 expression in vivo
Summary
Ovarian cancer is an aggressive tumor in women with high mortality. Paclitaxel (PTX) can be used for the chemotherapy of ovarian cancer. Many processes have been achieved in therapy, the prognosis of ovarian cancer patients is still poor. Deeply understanding the mechanism related to PTX resistance is necessary for improving the unfavorable prognosis of ovarian cancer patients. Circ_0051240 facilitated cell proliferation and tumor metastasis via sponging miR-637 in ovarian cancer [10]. Considerable evidence has suggested that circ_0063809 silencing and enforced expression of circEXOC6B sensitize ovarian cancer cells to PTX [11, 12]. Previous study has disclosed that circ_0061140 expression is increased in ovarian cancer cells, and its silencing hinders cell proliferation and migration [13]. The effects and regulatory mechanism of circ_0061140 in PTX sensitivity of ovarian cancer remain still unknown
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