Circ_03955 promotes pancreatic cancer tumorigenesis and Warburg effect by targeting the miR-3662/HIF-1α axis.

OBJECTIVES

Former studies found that circRNAs play an important part in the occurrence of a variety of malignant biological characteristics that are critical for cancer progression. It has been shown that circ_03955 is highly expressed and implicated with quantities of biological processes in solid tumor. However, whether circ_03955 regulates the tumorigenesis and Warburg effect of pancreatic cancer (PC) remains largely unknown.

MATERIALS AND METHODS

The level of circ_03955 in PC tissues and cell lines was determined by real-time qPCR (RT-qPCR). Loss-of-function and gain-of-function assays were employed to investigate the biological role of circ_03955 in cell proliferation, apoptosis, and glycolysis. RT-qPCR, western blotting, bioinformatics analysis, luciferase reporter assay, and in vivo tumorigenicity assay were employed to determine the underlying mechanisms.

RESULTS

In this study, it was investigated that circ_03955 was up-regulated in PC clinical samples as well as PC cell lines and associated with poor clinical outcomes of PC patients. Functional assays revealed that circ_03955 exerts a certain stimulative effect on the growth of PC cells in vitro and in vivo. Circ_03955 also inhibited apoptosis and promotes Warburg effect in PC cells. Mechanistically, bioinformatics analysis indicated that circ_03955 acts as a sponge for microRNA (miR)-3662, and hypoxia-inducible factor 1ɑ (HIF-1ɑ) was one of the transcriptional targets of miR-3662. Importantly, genetic promoting of HIF-1ɑ or downregulation of miR-3662 largely compromised circ_03955 depletion mediated tumor-inhibiting effects.

CONCLUSIONS

Taken together, circ_03955 functions as a tumor promoter through miR-3662/HIF-1α axis, which might provide a novel sight for PC treatment.