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  • Title: Circular RNA ciRS-7 promotes the proliferation and metastasis of pancreatic cancer by regulating miR-7-mediated EGFR/STAT3 signaling pathway.
    Author: Liu L, Liu FB, Huang M, Xie K, Xie QS, Liu CH, Shen MJ, Huang Q.
    Journal: Hepatobiliary Pancreat Dis Int; 2019 Dec; 18(6):580-586. PubMed ID: 30898507.
    Abstract:
    BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most deadly type of tumor, and its pathogenesis remains unknown. Circular RNAs (circRNAs) may be functional and bind to microRNAs and consequently, influence the activity of targeted mRNAs. Recent researches indicate that one circRNA, ciRS-7, acts as a sponge of miR-7 and thus, inhibits its activity. It is well known that miR-7 is a cancer suppressor in many cancers. However, the relationship between ciRS-7 and miR-7, and the role of ciRS-7 in PDAC, remains to be elucidated. METHODS: miR-7 and ciRS-7 expression in 41 pairs of PDAC tumors and their paracancerous tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between their expression levels and clinicopathological features in PDAC tissues were assessed. The relationship between miR-7 and ciRS-7 was also assessed by Spearman's correlation. We also used cell lines to evaluate the role of ciRS-7 in cell line behavior. The ciRS-7 interfere RNA (siRNA) and its empty vector were transfected into PDAC cells. PDAC cells proliferation and invasion abilities were detected by MTT assay and invasion analysis. The expression of proteins was assessed by Western blotting. RESULTS: ciRS-7 expression was significantly higher in PDAC tissues than paracancerous tissues (P = 0.002). However, miR-7 expression showed the opposite trend (P = 0.048). Moreover, ciRS-7 expression was inversely correlated with miR-7 in PDAC (rs = -0.353, P = 0.023). ciRS-7 expression was also significantly elevated in venous invasion (3.72 ± 2.93 vs. 2.14 ± 1.26; P = 0.028) and lymph node metastasis (4.19 ± 2.75 vs. 2.32 ± 1.90; P = 0.016) in PDAC patients. Furthermore, ciRS-7 knockdown suppressed cell proliferation and invasion of PDAC cells (P < 0.05), and the downregulation of ciRS-7 resulted in miR-7 overexpression and subsequent inhibition of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3). CONCLUSIONS: Circular RNA ciRS-7 plays an oncogene role in PDAC, partly by targeting miR-7 and regulating the EGFR/STAT3 signaling pathway.
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