Abstract
Hypoxia is one of the hallmarks of solid tumors, especially in hepatocellular carcinoma (HCC). CircRNAs are reported to be tightly connected to hypoxia and also have essential roles in cancer progression. However, many circRNAs implicated in hypoxia-mediated HCC progression are still unclear and require further exploration. In this study, a hypoxia cell model was structured by exposing cells to hypoxia conditions (1% O2) and normoxia conditions (21% O2) as a control. The effects of hypoxia and normoxia on cell viability, migration, invasion, and glycolysis were examined. The expressions of circRNARTN4IP1 under hypoxia were identified. Finally, molecular mechanisms and biological function of circRTN4IP1 were explored. We confirmed that hypoxia treatment facilitated capacities of proliferation, migration, invasion, and glycolysis in tumor cells. Hypoxia induced a significant increase expression of circRTN4IP1 in cells. Functionally, knockdown of circRTN4IP1 inhibited cell malignant progression and glycolysis under hypoxia HCC cells. Mechanistically, HIF1A targeted the promoter region of circRTN4IP1 and positively regulated the expression of circRTN4IP1. In addition, circRTN4IP1 targeted miR-532-5p/G6PC3 axis. In short, hypoxia induced activation of the HIF1A/circRTN4IP1/miR-532-5p/G6PC3 signaling axis, which promoted proliferation, migration, invasion, and glycolysis of HCC cells. This study may reveal a possible mechanism driving the progression of hypoxia HCC, so as to find potential effective candidates for targeting hypoxia microenvironment therapy.
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The data used to support the findings of this study are available from the corresponding author upon request.
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XY and CL designed the study, and drafted the manuscript. CY collected the clinical data and processed statistical data. QZ analyzed and interpreted the data. GL and YD partly contributed to the experiment. CY and QZ designed, supervised the study, and revised the manuscript. All authors read and approved the final version of the manuscript.
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Yang, X., Lou, C., Zhang, Q. et al. Hypoxia-induced circRTN4IP1 promotes progression and glycolysis of hepatocellular carcinoma cells. Funct Integr Genomics 23, 339 (2023). https://doi.org/10.1007/s10142-023-01256-0
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DOI: https://doi.org/10.1007/s10142-023-01256-0