Upregulated circular RNA circ_0030235 predicts unfavorable prognosis in pancreatic ductal adenocarcinoma and facilitates cell progression by sponging miR-1253 and miR-1294

Accumulating evidence indicated that dysregulated circular RNAs (circRNAs) could play pivotal roles in cancer biology. A recent study demonstrated that circ_0030235 expression is upregulated in human pancreatic ductal adenocarcinoma (PDAC) by high-throughput circRNA microarray. In the current work, we aimed to elucidate the clinical significance, prognostic value, functional roles and mechanism of circ_0030235 in PDAC. Quantitative real time-PCR was used to detect circ_0030235 expression in PDAC tissue specimens and cell lines. The clinical significance of circ_0030235 was evaluated by Fisher's exact test, Kaplan-Meier curves, and Cox regression analysis. Cell growth, apoptosis, and metastatic properties were then explored after circ_0030235 knockdown/overexpression. Dual luciferase reporter assay was applied to detect the mechanisms of circ_0030235. As a result, the data documented that circ_0030235 was upregulated in PDAC cell lines and cancerous tissues compared with HPDE and matched normal tissue specimens, respectively. Overexpression of circ_0030235 in tumor samples is related to higher tumor stage and positive lymph node invasion. Additionally, analyses documented that high expression of circ_0030235 was associated with poor prognosis for PDAC patients. Knockdown of circ_0030235 by siRNAs inhibited cell growth, migratory and invasive potential, and promoted cell apoptosis. On the contrary, overexpression of circ_0030235 caused the opposite effect. Mechanistically, circ_0030235 directly sponges miR-1253 and miR-1294 in PDAC cells. What's more, the oncogenic properties of circ_0030235 was partly dependent on its suppression on miR-1253 and miR-1294. Overall, the results showed that circ_0030235 might act as an effective therapeutic target and indicate dismal prognosis for PDAC. (C) 2018 Elsevier Inc. All rights reserved.