Hypoxia-induced circRNF13 promotes the progression and glycolysis of pancreatic cancer

Pancreatic cancer (PC) is one of the most malignant tumors. Rapid progression and distant metastasis are the main causes of patient death. Hypoxia is a hallmark of multiple cancers and is involved in tumor biology. However, little is known about the roles of circRNAs in glycolysis and hypoxia-mediated progression of PC. Here, the expression pattern of hypoxia-related circRNAs was analyzed using RNA sequencing. A unique circRNA termed circRNF13 was found to be upregulated in PC tissues and may be a potential prognostic indicator. HIF-1 alpha and EIF4A3 are involved in regulating the biogenesis of circRNF13. Furthermore, circRNF13 was validated to exert a stimulative effect on cell proliferation, angiogenesis, invasion and glycolysis. Importantly, we found that circRNF13 promoted PDK3 levels by acting as a miR-654-3p sponge, thus promoting the PC malignant process. Collectively, our results reveal that hypoxia-induced circRNF13 mediated by HIF-1 alpha and EIF4A3 promotes tumor progression and glycolysis in PC, indicating the potential of circRNF13 as a prognostic biomarker and therapeutic target for PC. Cancer: circular RNA in pancreatic tumor progression The low-oxygen (hypoxic) conditions within pancreatic tumors promote production of a newly identified circular RNA molecule associated with aggressive tumor growth. Pancreatic cancers are generally difficult to treat, and the hypoxic conditions of the tumor interior are known to contribute to greater resistance to chemotherapy. Several studies have indicated that these conditions also lead to greater production of certain circular RNAs, and researchers led by Rong Wan at Shanghai Jiao Tong University School of Medicine, China, set out to identify specific RNA molecules produced within hypoxic pancreatic tumor tissue. Biopsy samples containing high levels of one such RNA, circRNF13, were consistently linked with a poor prognosis. The researchers also identified downstream targets modulated by circRNF13 that contribute to progression, which could offer new targets for drug development.

Automated summary

This research reveals that the hypoxic conditions within pancreatic tumors promote the production of a circular RNA molecule called circRNF13, which is associated with aggressive tumor growth. High levels of circRNF13 are linked to a poor prognosis and it modulates downstream targets that contribute to tumor progression, providing new targets for drug development.