Abstract
Circular RNAs (circRNAs) play important roles in cancer tumorigenesis and progression, representing prognostic biomarkers and therapeutic targets. In this case, we demonstrated the role of circ-NOLC1 in epithelial ovarian cancer (EOC). Our results have shown that Circ-NOLC1 expression was higher in EOC tissues than in normal tissues, and was positively associated with FIGO stage, differentiation. Among ovarian cancer cell lines, circ-NOLC1 expression was the highest in A2780, and lowest in CAOV3. Overexpression of circ-NOLC1 in CAOV3 cells increased cell proliferation, migration, and invasion ability, whereas silencing of circ-NOLC1 in A2780 cells had the opposite effect: however, neither circ-NOLC1 downregulation nor overexpression influenced NOLC1 mRNA expression. In nude mice with subcutaneous tumors, circ-NOLC1 downregulation decreased tumor growth. Bioinformatic analysis and RNA-binding protein immunoprecipitation showed that circ-NOLC1 could bind to ESRP1. In addition, the overexpression of circ-NOLC1 significantly increased ESRP1, RhoA, and CDK1 protein and mRNA expression level; circ-NOLC1 downregulation had the opposite effects. The tumor-promoting effect of circ-NOLC1 was inhibited by knockdown of ESRP1, CDK1, or RhoA expression in circ-NOLC1-overexpressing cells, which might act by modulating RhoA and CDK1 expression. In conclusion, our study demonstrated that Circ-NOLC1 might promote EOC tumorigenesis and development by binding ESRP1 and modulating CDK1 and RhoA expression.
Highlights
Ovarian cancer is a malignant tumor that seriously threatens women’s health[1–3]
The results showed that circ-NOLC1 expression was significantly higher in borderline and ovarian cancers than in normal and benign ovarian tissues (Fig. 1A, p < 0.05, Table 1)
The expression of circ-NOLC1 was higher in CA125 positive (>35 U/ml) ovarian cancer patients (Fig. 1D, *p < 0.05, Table 2). These results suggested that circ-NOLC1 involves in the tumorigenesis and progression of ovarian cancer, and may have potential to be treated as diagnostic biomarker
Summary
Ovarian cancer is a malignant tumor that seriously threatens women’s health[1–3]. Asymptomatic clinical appearance in the disease’s progression, resulting in widespread disease in the pelvic and abdominal cavity. Even though surgery, chemotherapy, and biological therapy are used widely to treat ovarian cancer, the 5-year survival rate remains at only 35–38%4,5. The occurrence and development of ovarian cancer is a complex process, comprising multi-step, multi-gene, and multi-factor regulations, especially the regulation of transcription factor regulatory networks, signaling pathways, and regulatory loops. Recent studies have shown that non-coding RNAs play an important role in the process of ovarian cancer proliferation, apoptosis, invasion, and metastasis[6]. Non-coding RNAs are RNA molecules in the transcriptome that are not translated into proteins, including small nuclear RNAs, small nucleolar RNAs, microRNAs with relatively small molecular weight (miRNAs), piwiinteracting RNAs, long non-coding RNAs, and circular
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