Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR‐625 and miR‐892b

• Published in: Journal of cellular biochemistry Vol. 120; no. 3; pp. 3780 - 3789
• Main Authors: Hao, Liguo, Rong, Wei, Bai, Lianjie, Cui, Hongsheng, Zhang, Shuli, Li, Yuanchun, Chen, Datong, Meng, Xin
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2019
• Subjects: Adenocarcinoma; Apoptosis; Assaying; Biomarkers; Biotechnology; Caspase; Cell growth; Cell migration; Cell proliferation; circ_0007534; Circular RNA; Invasiveness; Lymph nodes; Metastases; miR‐625; miR‐892b; Pancreas; Pancreatic cancer; pancreatic ductal adenocarcinoma; Polymerase chain reaction; Regulators; Ribonucleic acid; RNA; Tissues; Xenografts; Xenotransplantation; miR-892b; circ_0007534; circular RNA; miR-625; pancreatic ductal adenocarcinoma
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27658

Circular RNAs (circRNAs) have been regarded as critical regulators of human diseases and biological markers in some types of malignancies, including pancreatic ductal adenocarcinoma (PDAC). Recently, circ_0007534 has been identified as a novel cancer‐related circRNA. Nevertheless, its clinical relevance, functional roles, and mechanism have not been studied in PDAC. In the current study, real‐time quantitative polymerase chain reaction (RT‐qPCR) was used to detect the expression of circ_0007534 in 60‐paired PDAC tissue samples and different cell lines. Loss‐of‐function and gain‐of‐function assays were performed to detect cell proliferation, apoptosis, and metastatic properties affected by circ_0007534. An animal study was also carried out. The luciferase reporter assay was performed to uncover the underlying mechanism of circ_0007534. As a result, circ_0007534 was overexpressed not only in PDAC tissues but also in a panel of PDAC cell lines, and this overexpression is closely associated with advanced tumor stage and positive lymph node invasion. In addition, circ_0007534 may be regarded as an independent prognostic factor for patients with PDAC. For the part of functional assays, circ_0007534 significantly increased cell proliferation, migratory, and invasive potential of PDAC cells. Circ_0007534 could inhibit cell apoptosis partly via a Bcl‐2/caspase‐3 pathway. The xenograft study further confirmed the cell growth promoting the role of circ_0007534. Mechanistically, miR‐625 and miR‐892b were sponged by circ_0007534. The oncogenic functions of circ_0007534 is partly dependent on its regulation of miR‐625 and miR‐892b. In conclusion, our study illuminates a novel circRNA that confers an oncogenic function in PDAC. Circ_0007534 is upregulated in pancreatic ductal adenocarcinoma (PDAC) both in tissues and cells. Circ_0007534 is associated with patients’ adverse phenotypes and poor survival. The circ_0007534/miR‐625/miR‐892 regulatory axis may contribute to the carcinogenesis and development of PDAC.